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1 Chapter 1Figure 1.1 Classes of proteins associated with human genetic diseases.

2 Chapter 2Figure 2.1 Data integration strategy for Monarch. Data, mainly “genotype‐to‐...Figure 2.2 The Mouse Models of Human Cancer Database (MMHC), formerly Mouse ...Figure 2.3 IMPC phenotyping pipelines for adult mice (17 weeks) and embryos...Figure 2.4 The histopathology browser for the IMPC database. Data can be sea...

3 Chapter 3Figure 3.1 Top, searching p53 SNPs reveals “The gene you selected is not in ...Figure 3.2 Finding the gene and allele symbol on Mouse Genome Informatics. O...Figure 3.3 Current symbols assigned to a variety of unrelated genes original...Figure 3.4 Nomenclature for hybrid stocks.Figure 3.5 Setting up a mapping cross using F1 and F2 hybrids.Figure 3.6 Crossing AKR/J mice with more than one inbred strain to map the m...Figure 3.7 Using recombinant inbred lines to narrow candidate gene intervals...

4 Chapter 4Figure 4.1 Nonhuman (including mouse) models were historically compared empi...Figure 4.2 Human population response to disease is often highly variable bet...Figure 4.3 Effect of strain on phenotype for a single gene mutation. A class...Figure 4.4 Mouse models identify subtypes of junctional epidermolysis bullos...Figure 4.5 Fitting mouse models to the concepts of human disease. The mouse ...Figure 4.6 Validation of mouse models over time. In 1989 few mouse models ac...

5 Chapter 5Figure 5.1 Composite image of embryonic mouse developmental stages from just...Figure 5.2 Mouse embryo littermates with a shared chronological age at gesta...Figure 5.3 The early placenta (shown here at GD8.5) consists chiefly of mate...Figure 5.4 The definitive placenta forms fully by GD12.5 (Panel (a)), appear...Figure 5.5 The labyrinth of the placenta (shown here for wild‐type CD‐1 mice...Figure 5.6 The nascent metrial gland (also designated the mesometrial lympho...Figure 5.7 Noninvasive imaging modalities are useful means for characterizin...Figure 5.8 Sex differentiation of neonatal (PND1) mice using anogenital dist...Figure 5.9 Schematic diagram showing necropsy approach for neonatal and juve...Figure 5.10 Sectioning (Wilson's) technique to allow macroscopic evaluation ...Figure 5.11 Sectioning (Wilson's) technique to allow macroscopic evaluation ...Figure 5.12 Skeletal double staining may be used to characterize axial patte...Figure 5.13 Developmental anatomy of a wild‐type GD16.0 mouse embryo demonst...Figure 5.14 Missing structures represent a special situation in developmenta...Figure 5.15 Comparison of variable lesion progression in three litters of wi...Figure 5.16 Developmental phenotypes resulting from circulatory disturbances...Figure 5.17 Embryonic death is demonstrated by a spectrum of macroscopic and...Figure 5.18 A common cause of neonatal lethality is inability to suckle, whi...Figure 5.19 An outcome‐oriented decision tree for evaluating embryonic letha...Figure 5.20 An outcome‐oriented decision tree for evaluating neonatal and ju...Figure 5.21 Placental dysfunction relative to wild‐type littermates (left co...Figure 5.22 Schematic representation of structurally distinct lesion pattern...Figure 5.23 Common lesions in the placental labyrinth of mouse embryos may a...

6 Chapter 6Figure 6.1 Nasal epithelium. Motile cilia are present on respiratory epithel...Figure 6.2 Brain hydrocephalus. Ependymal ciliary dysfunction often results ...Figure 6.3 Epididymis. Flagellar defects or dysfunction are common causes of...Figure 6.4 Polycystic kidney disease. Dilatation of renal tubules in an enla...Figure 6.5 Nephronophthisis. Cystic tubules with interstitial inflammation a...Figure 6.6 Eye. Macrophages within the outer segment of photoreceptor are pr...Figure 6.7 Eye. Advanced retinal degeneration there is characterized by a ma...

7 Chapter 7Figure 7.1 Bone marrow. Bone marrow hypoplasia four days after deletion of C...Figure 7.2 Thymus. (a, b). Medulla of thymus of a female C57BL/6J mouse (a) ...Figure 7.3 Lymph nodes. C57BL/6J (a–c), B6.Cg‐Foxn1nu (d–f), B6.129S7‐Rag1tm...Figure 7.4 Amyloid. (a) Amyloid in mesenteric lymph node of 615‐day old C57B...Figure 7.5 Mucosal lymphoid tissues. (a) Peyer's patch in C57BL/6 J mouse. (...Figure 7.6 Spleen. Spleen of C57BL/6J (a), B6.Cg‐Foxn1nu (b), B6.129S7‐Rag1t...Figure 7.7 Melanin vs. hemosiderin. (a) Spleen of B6.Cg‐Prkdcscid/SzJ mouse ...Figure 7.8 Tertiary lymphoid structures. Tertiary lymphoid tissue with two f...

8 Chapter 8Figure 8.1 Monocytic leukemia, H&E. Spleen with blasts and immature form...Figure 8.2 Monocytic leukemia, IHC. The cells in Figure 8.1 express the mono...Figure 8.3 Erythroleukemia, H&E. Bone marrow with blasts and differentia...Figure 8.4 Erythroleukemia, IHC. The more differentiated cells in Figure 8.3...Figure 8.5 Mast cell leukemia, H&E. Spleen with small and large cells wi...Figure 8.6 Mast cell leukemia, IHC. The cells in Figure 8.5 express CD117 (C...Figure 8.7 Follicular lymphoma, H&E. Lymph node with an abundance of cen...Figure 8.8 Follicular lymphoma, IHC. The neoplastic cells in Figure 8.7 expr...Figure 8.9 DLBCL, anaplastic variant, H&E. This lymphoma variant has hal...Figure 8.10 DLBCL, anaplastic variant, IHC. The neoplastic cells in Figure 8...Figure 8.11 Diffuse high‐grade blastic B‐cell lymphoma, H&E....Figure 8.12 Diffuse high‐grade blastic B‐cell lymphoma, IHC. The...Figure 8.13 Peripheral T‐cell lymphoma (PTCL), small cell, H&E. A ...Figure 8.14 PTCL, small cell, IHC. The neoplastic cells in Figure 8.13 expre...Figure 8.15 PTCL, small cell, H&E. A splenic lymphoma with a monomorphic...Figure 8.16 PTCL, small cell, IHC. The neoplastic cells in Figure 8.15 expre...Figure 8.17 PTCL, large cell, H&E. A splenic lymphoma with a monomorphic...Figure 8.18 PTCL, large cells, IHC. The neoplastic cells in Figure 8.17 expr...

9 Chapter 9Figure 9.1 Kidney of a CB17.Cg‐PrkdcscidLystbg‐J/Crl mouse. Rena...Figure 9.2 Representative sections of lymphoid organs. The spleen (a), thymu...Figure 9.3 Representative sections of spleen. The spleen of NOD.Cg‐PrkdcscidFigure 9.4 Representative sections of lymph node. The cortical and medullary...Figure 9.5 Heterotopic implantation (subcutis). A patient‐derived lymphoma i...Figure 9.6 Bone marrow of a NOD.Cg‐PrkdcscidIl2rgtm1Wjlmouse engrafted...Figure 9.7 Skin of a NOD.Cg‐PrkdcscidIl2rgtm1Wjlmouse. Inflammatory ce...Figure 9.8 Diffuse large B cell lymphoma of human origin that occurred at th...Figure 9.9 Bone marrow failure with secondary septicemia after irradiation a...Figure 9.10 Kidney with inclusion body nephropathy caused by mouse kidney pa...Figure 9.11 Macroscopic appearance of the gastrointestinal tract in a NOD.Cg...Figure 9.12 Superficial necrotizing colitis caused by C. difficile. Multifoc...Figure 9.13 Naturally occurring Candida glabrata infection in the brain of a...Figure 9.14 Demodex musculi infestation in a NOD.Cg‐PrkdcscidIl2rgtm1W...Figure 9.15 Natural mammalian orthoreovirus infection in a NOD.Cg‐Prkdc...Figure 9.16 Pneumocystis murina infection in a NOD.Cg‐PrkdcscidIl2rgtm...Figure 9.17 Naturally occurring glomerulonephritis in an athymic nude mouse,...

10 Chapter 10Figure 10.1 Embryonic hair follicle development. The epidermis is relatively...Figure 10.2 Gross differences in hair cycle stage. An agouti C3H/HeJ shaved ...Figure 10.3 Major stages of the hair cycle in adult C57BL/6NJ mice. While su...Figure 10.4 Evaluation of plucked hair. Hair can be manually plucked from a ...Figure 10.5 Vibrissae and tail hair follicles. Vibrissae follicles (A–C) are...Figure 10.6 Specialized hairs and nail. Cilia (c) in the eyelid have their o...Figure 10.7 Normal late anagen truncal hair follicle. Low magnification (A) ...Figure 10.8 Commonly used markers for skin. Smooth muscle actin (SMA) is a g...Figure 10.9 Interdigitation of the cuticle layers. The cuticle of the inner ...Figure 10.10 Selecting ages for phenotyping. Set ages based on normal develo...Figure 10.11 Disease progression of alopecia areata. Full thickness skin gra...Figure 10.12 Disease progression of dermatitis in Sharpin cpdm mice. Mutan...Figure 10.13 Proliferation rates of skin. Brown labeled nuclei in a Sharpinc...Figure 10.14 Horizontal sections. Most skin sections are evaluated as vertic...Figure 10.15 Zymbal's gland. The Zymbal's gland is located at the base o...Figure 10.16 Primary cicatricial (scarring) alopecia. A number of mutations ...Figure 10.17 B6 alopecia and dermatitis. C57BL/6 substrains are prone to dev...Figure 10.18 Hairless allelic mutations. B6.Cg mice homozygous for the hairl...Figure 10.19 Excessive hair growth. The angora (a, C57BL/6J‐Fgf5go top, wild...Figure 10.20 Follicular dystrophy genocopies. Severe twisting of weak, defor...Figure 10.21 Hair structural defects. Mice carrying a mutation in the desmop...Figure 10.22 Alopecia areata. Bald patches of skin are evident on the dorsal...Figure 10.23 Spontaneous trichepithelioma in an HRS/J male. Multiple cysts f...Figure 10.24 Spontaneous papillomas in mice. Spontaneous papillomas are foun...Figure 10.25 Spontaneous squamous cell carcinoma. An aggressive squamous cel...Figure 10.26 Spontaneous nonmelanoma skin cancer. Some mutant strains, such ...Figure 10.27 UV light‐induced skin tumors. Outbred Crl:SKH1‐Hrhr hairl...Figure 10.28 Mouse papillomavirus (MmuPV1) infection. MmuPV1 causes benign p...Figure 10.29 Spontaneous pigmented epithelioid melanocytoma. Melanomas very ...Figure 10.30 Pemphigus vulgaris. Blister formation within the epidermis and ...Figure 10.31 Junctional epidermolysis bullosa. The Lamc2jeb/jeb hypomorphic ...Figure 10.32 Nail dystrophy with rotation of P3 in NON/ShiLtJ mice. A common...Figure 10.33 Subungual intraosseous cysts in old mice. This is a rare sponta...

11 Chapter 11Figure 11.1 The test by transplantation. Transplantation in orthotopic or ec...Figure 11.2 Whole Mount Subgross and Histology. Whole slide images of the le...Figure 11.3 Invasion vs. Expansion. These images illustrated growth patterns...Figure 11.4 Metastasis. These images illustrate various sites and modes of m...Figure 11.5 Rogues Gallery of GEM tumor phenotypes. Each image is selected t...Figure 11.6 Other GEM Phenotypes. (a) Papillary mammary tumor from a GEM Not...Figure 11.7 Case study. (a‐b) LS‐TAFI 3D image of a Stat1 null terminal end ...Figure 11.8 Human‐mouse comparisons. Although the biology of mouse mam...Figure 11.9 Mammary Intraepithelial Neoplasia (MIN). This figure illustrates...Figure 11.10 Case study. (a) A histological image of an HE stained Stat1 KO ...

12 Chapter 12Figure 12.1 Nasal hyalinosis. Eosinophilic protein inclusions and a few intr...Figure 12.2 Massive nasal poxvirus infection of the nasal cavity. [10]. Intr...Figure 12.3 Whole lung infused with formalin. Left, right, and accessory lob...Figure 12.4 iBALT in mouse lung. Perivascular and bronchiolar lymphoid nodul...Figure 12.5 Perfused lung embedded with heart. Note lobes shown are uniforml...Figure 12.6 Individual lung lobes for embedding. The fixed lung lobes were i...Figure 12.7 SCGB1A1 in bronchiolar club cells. The club cell antigen is pres...Figure 12.8 Gross necropsy findings of pulmonary hyalinosis (crystalline pne...Figure 12.9 Whole lung section with crystalline pneumonia. The lesions are d...Figure 12.10 Early lung lesions of an Ncf1 m1J homozygous mutant mouse. Th...Figure 12.11 CHIL3 in alveolar macrophages. Early lesions of hyalinosis in a...Figure 12.12 Alveolar macrophages in a Lat tm1Les homozygous mutant mouse....Figure 12.13 Alveolar macrophages in an Ncf1 m1J homozygous mutant mouse. ...Figure 12.14 Alveolar macrophages in an Ncf1 m1J homozygous mutant mouse. ...Figure 12.15 Electron micrograph of the CHIL3 crystals. Note the thin needle...Figure 12.16 Foreign material in bronchiole. After intranasal administration...Figure 12.17 Centrilobular distribution of induced inflammatory lesions. Nin...Figure 12.18 Lobular distribution of induced lesions. Fifteen days postnasal...Figure 12.19 Diffuse distribution of induced lesions. Five days postnasal in...Figure 12.20 Viral antigen in bronchiolar epithelium. SARS CoV in bronchiola...Figure 12.21 Viral antigen in bronchiolar club cells and alveolar cells. Day...Figure 12.22 H5N1 influenza viral antigen in lung. Day 2 after infection in ...Figure 12.23 Acute viral lesions in a bronchiole. There is necrosis of bronc...Figure 12.24 Bronchiolar hyperplasia. Hyperplastic club cells after naturall...Figure 12.25 Viral antigen in alveolar cells. Mice infected with pneumonia v...Figure 12.26 Interstitial pneumonia. Alveolar walls are thickened, and infla...Figure 12.27 Alveolar bronchiolization. Naturally‐occurring chronic Sendai v...Figure 12.28 Migration of leukocytes from arteriole into lung. Leukocytes ar...Figure 12.29 Vasculitis. Migration (arrows) of CD3+ lymphocytes through wall...Figure 12.30 Pyogranuloma in the lung. A large lesion with central necrosis ...Figure 12.31 SARS CoV antigen in macrophages in a pyogranuloma as in Figure ...Figure 12.32 Ectopic mineralization. Foci of mineralization can be found sca...Figure 12.33 Club cell mucous metaplasia. Note the variable mucus in each cl...Figure 12.34 PAS stain of club cell mucous metaplasia. OVA model with peribr...Figure 12.35 Fibrosis, alveolar. Masson's trichrome stain shows abundant col...Figure 12.36 Hyperplasia, alveolar. Alveolar Type II cell (AT2) hyperplasia ...Figure 12.37 Hyperplasia, alveolar Type II cells (AT2). TTF1 antigen (NKX2‐1...Figure 12.38 Adenoma, alveolar Type II cell (AT2). The tumor cells are unifo...Figure 12.39 Adenocarcinoma (right side) in an adenoma. Note the papillary l...Figure 12.40 Cell proliferation in the adenocarcinoma developing in an adeno...Figure 12.41 Alveolar Type II cell (AT2) antigen (SFTPD). The antigen can be...Figure 12.42 Papillary bronchiolar hyperplasia. Multiple lesions in the bron...Figure 12.43 SCGB1A1 antigen in papillary hyperplasia. Note the adenoma and ...Figure 12.44 SCGB1A1 antigen in bronchioles. Note lack of labeling in adenom...Figure 12.45 Adenocarcinoma. Solid and papillary patterns can be seen.Figure 12.46 Squamous metaplasia. Squamous lesions in bronchiole and alveoli...Figure 12.47 Neuroendocrine carcinoma. Small cell carcinoma in a mutant mous...Figure 12.48 Metastatic liver tumors in lung. Note many tumor nodules of var...

13 Chapter 13Figure 13.1 Trimming and embedding protocol for mouse stomach. The stomach i...Figure 13.2 Example of 6 normal stomach sections from one mouse on one slideFigure 13.3 Stomach from mouse with diffuse and focal gastric proliferative ...Figure 13.4 Mouse stomachs with several glandular stomach hyperplastic plaqu...Figure 13.5 Hyalinosis in glandular stomach. There are intracellular and ext...Figure 13.6 Gastric crystals. The CHIL3‐containing gastric crystals of vario...Figure 13.7 Gastric yeast. Many yeast, Kazachstania pintolopesii, are seen o...Figure 13.8 Glandular stomach. Chronic gastritis with diffuse epithelial hyp...Figure 13.9 Glandular stomach. Mucus metaplasia, diffuse in hyperplastic gas...Figure 13.10 Glandular stomach. Focal gastric dysplasia in chronic gastritis...Figure 13.11 Glandular stomach antrum. Diffuse gastric hyperplasia and pylor...Figure 13.12 Glandular stomach. Single large gastric adenoma at the transiti...Figure 13.13 Gastric adenocarcinoma invading through the layers of the stoma...Figure 13.14 Forestomach. Squamous cell carcinoma.Figure 13.15 Pylorus. Atypical adenomatous hyperplasia with epithelial herni...Figure 13.16 Gastric herniation. Arising as hyperplastic glands grow through...Figure 13.17 Small intestinal gut roll. Multiple lesions (dysplasias, microa...Figure 13.18 Large intestinal gut roll. It is closed (a) and opened (b) with...Figure 13.19 Colitis trim protocol. The first two sections of descending col...Figure 13.20 Colon. Gross appearance of colon adenomas (polyps), azoxymethan...Figure 13.21 Colon. Focus of dysplasia. One crypt is involved.Figure 13.22 Small intestine. Focal dysplasia, multiple crypts. Hyperchromas...Figure 13.23 Colon. Multifocal hyperplasia with dysplasia in a regenerative ...Figure 13.24 Focus of colonic regenerative hyperplasia in induced colitis mo...Figure 13.25 Small intestine. Microadenoma, with high‐grade dysplasia.Figure 13.26 Small intestine. CTNNB1 in focal dysplasia. Nuclear staining in...Figure 13.27 Small intestine. CTNNB1 in dysplasia. Note the nuclear and cyto...Figure 13.28 Small intestine, adenoma, sessile. No invasion is seen.Figure 13.29 Comparative histogenesis of colon adenocarcinoma in humans (top...Figure 13.32 Adenocarcinoma, small intestine, mouse. Invasion to the serosa....Figure 13.33 Colon. Adenocarcinoma, mucinous, with cystic mucinous areas in ...Figure 13.34 Colon. High magnification of 13.33 showing the cystic areas dev...Figure 13.35 Colon. Diffuse invasive adenocarcinoma showing muscle and lymph...Figure 13.36 Cecum, gastrointestinal stromal tumor (GIST) in a mutant mouse....Figure 13.37 Colon hamartoma in a Cdx2 tm1Mmt mouse. The cystic proliferat...

14 Chapter 14Figure 14.1 Longitudinal section of HE stained heart from a NZW/LacJ mouse d...Figure 14.2 Cross section of Masson's trichrome stained normal large elastic...Figure 14.3 Normal mouse medium pulmonary vein with abundant striated cardia...Figure 14.4 Cross section of Masson's trichrome stained normal medium muscul...Figure 14.5 Transverse sections of the heart can be performed at mid papilla...Figure 14.6 Longitudinal section of HE stained normal heart showing the LVFW...Figure 14.7 Atherosclerosis lesion stained with Oil Red O for image quantifi...Figure 14.8 Heart, aorta, and branches from a normal mouse. The mouse was pe...Figure 14.9 Cross section of a Movat's pentachrome stained medium muscular a...Figure 14.10 Wheat Germ Agglutinin (WGA) binds to glycoproteins of the cell ...Figure 14.11 Normal mice may have an os cordis within the annulus fibrosus s...Figure 14.12 Polyarteritis Nodosa is a common background lesion in a number ...Figure 14.13 Gross (a) and histologic (b) images of epicardial mineralizatio...Figure 14.14 Gross image of a large pale thrombus in the atrium (a) creating...Figure 14.15 Longitudinal section of Masson's trichrome stained heart. The a...Figure 14.16 Oblique cross section of HE stained aortic valve showing numero...Figure 14.17 Abundant fibrin with enmeshed degenerate neutrophils and large ...Figure 14.18 Spontaneous hemangiosarcoma characterized by poorly formed vasc...Figure 14.19 Masson's trichrome stain demonstrating abundant replacement fib...Figure 14.20 HE stain of myocardial necrosis with infiltration of numerous n...Figure 14.21 HE stain from a mouse with arteriolosclerosis with a narrowed l...Figure 14.22 Florid pulmonary hypertension lesions in a transgenic mouse wit...Figure 14.23 In this HE stain, the aortic root has a mononuclear infiltrate ...Figure 14.24 HE staining of the aortic root from an B6.129P2‐Apoetm1Unc/J mo...

15 Chapter 15Figure 15.1 Role of hepatoblasts in liver. Differentiation of hepatoblasts i...Figure 15.2 Trimming the liver. How to obtain mouse liver sections for histo...Figure 15.3 HCC in mouse liver. Gross liver tumors in a two‐year‐old mouse. ...Figure 15.4 HCC in mouse liver. Liver masses in a Liver‐Onc3/HBsAg mouse. Mu...Figure 15.5 Liver microenvironment. The liver microenvironment is composed o...Figure 15.6 Connexin 32 (GJB1) immunostaining. Connexin 32 (GJB1) in the liv...Figure 15.7 Fibrosis/cirrhosis in mouse livers. Photomicrograph of the liver...Figure 15.8 Fatty change in mouse liver. Fatty change, centrilobular, mouse ...Figure 15.12 Fibrosis in mouse liver. Hepatic periportal fibrosis in a mouse...Figure 15.13 On the origin of liver cancer. Hepatocyte and Hepatic Progenito...Figure 15.14 Hepatocellular adenoma, basophilic with clear cells.Figure 15.15 Large hepatocellular adenoma with clear cell and lipid areas.Figure 15.16 Mouse liver parenchymal compression by adenoma. Edge of hepatoc...Figure 15.17 Mouse liver – trabecular hepatocellular carcinoma developing in...Figure 15.18 Mouse lung with metastases of hepatocellular carcinoma.Figure 15.19 Metastases of hepatocellular carcinoma in lung. Basophilic area...Figure 15.20 Hyaline droplets in pancreatic duct. Hyalinosis in an interlobu...Figure 15.21 Human PDAC. Human PDAC showing ductal morphological and extensi...Figure 15.22 Human PDAC – adenosquamous variant. Adenosquamous variant...Figure 15.23 Human and mouse PanIN. From left to right: PanIN1, 2 (both now ...Figure 15.24 Pancreatic remodeling. Remodeling of the acinar compartment of ...Figure 15.26 Acinar‐to‐ductal and mucinous metaplasia. Acinar‐to...Figure 15.27 Atypical flat lesion. Atypical flat lesion (AFL) (center) adjac...Figure 15.28 Ductular‐insular complex. Ductular‐insular complex (right...Figure 15.29 Mouse PDAC G2. Moderately differentiated PDAC in a Tg(Pdx1‐...Figure 15.30 Mouse PDAC G3. Poorly differentiated PDAC in a Tg(Pdx1‐cr...Figure 15.31 Sarcomatoid mouse PDAC. Sarcomatoid PDAC in a Tg(Pdx1‐cre...Figure 15.32 E‐cadherin expression in sarcomatoid mouse PDAC. Retained...Figure 15.33 Intravascular tumor cells. Tumor cell invasion into an intrapan...Figure 15.34 Pulmonary metastasis. Pulmonary metastasis of a PDAC in a Tg(Pd...Figure 15.35 Primary lung adenoma. Primary lung adenoma in a Tg(Pdx1‐c...

16 Chapter 16Figure 16.1 Mouse skeletal muscle. (a) Transverse section of spinal column s...Figure 16.2 Mouse spinal cord. (a) Artifactual vacuolization of neurons and ...Figure 16.3 Mouse quadriceps muscle. (a) Transverse section of wild‐type qua...Figure 16.4 Mouse skeletal muscleneurogenic myopathy. (a) Showing contras...Figure 16.5 Mouse spinal cordlower motor neurons. (a) “Ghost” motor neuro...Figure 16.6 Mouse spinal cord. (a) Luxol fast blue stain highlight reduced m...Figure 16.7 Mouse sciatic nerve. (a–c) Transverse sections show normal sciat...Figure 16.8 Mouse femoral nerve. (a, b) Longitudinal sections show normal ap...Figure 16.9 Mouse skeletal muscle – neuromuscular junction (NMJ). (a) ...Figure 16.10 Mouse skeletal muscle – muscle spindle. (a) Normal muscle...Figure 16.11 Mouse skeletal muscle – interosseous membrane and Pacinian corp...Figure 16.12 Mouse skeletal muscle – myogenic myopathy. (a) Internaliz...Figure 16.13 Mouse skeletal muscle – regeneration. (a) Regenerating fi...Figure 16.14 Mouse skeletal muscle – old male mice. (a) Prominent cont...Figure 16.15 Mouse skeletal muscle. (a) Centralized nuclei and ring fibers. ...Figure 16.16 Mouse skeletal muscle – autophagy myopathies. (a) Interna...

17 Chapter 17Figure 17.1 Pituitary gland in situ observed within the sella turcica upon r...Figure 17.2 Photomicrograph of the pituitary gland in situ overlying the bas...Figure 17.3 The pituitary gland is enlarged and red due to the presence of a...Figure 17.4 A focal adenoma (left) within the pars distalis is associated wi...Figure 17.5 Centrally, an adenoma of the pars intermedia is compressing the ...Figure 17.6 Bilaterally, the lobes of the thyroid gland are attached to the ...Figure 17.7 Diffuse bilateral follicular hyperplasia (goiter) secondary to i...Figure 17.8 Thyroid follicular hyperplasia and dysplasia characterized by co...Figure 17.9 Marked lymphocytic infiltrates are disrupting normal thyroid fol...Figure 17.10 Bilateral follicular thyroid carcinomas.Figure 17.11 Follicular thyroid carcinoma.Figure 17.12 Intravascular rafts of follicular thyroid carcinoma cells.Figure 17.13 Pulmonary metastasis of follicular thyroid carcinoma.Figure 17.14 Thyroid C cell adenoma.Figure 17.15 Chief cells within the parathyroid gland are widely separated b...Figure 17.16 Parathyroid chief cell adenoma.Figure 17.17 Bilateral regression of the adrenocortical X‐zone as evidenced ...Figure 17.18 Large macrophages containing yellowish‐brown pigment are associ...Figure 17.19 Subcapsular proliferation of type A spindle cells (right) and a...Figure 17.20 Focal pheochromocytoma at the cortical‐medullary junction that ...Figure 17.21 Aldehyde fuchsin histochemical staining of insulin within ß cel...Figure 17.22 Mouse islets of variable sizes can be organized in close proxim...Figure 17.23 Numerous hyperplastic and neoplastic islets distributed through...Figure 17.25 Hyperplastic and neoplastic islets in the pancreas of a Men1 he...Figure 17.26 The pineal gland is located dorsally in a coronal section of th...

18 Chapter 18Figure 18.1 Normal kidney. Longitudinal section shows cortex, medulla, papil...Figure 18.2 Normal kidney. Bowman capsule with flat or cuboidal epithelium i...Figure 18.3 Normal glomerulus. Vimentin (VIM) IHC. Note foot processes of po...Figure 18.4 Normal glomerulus. Kinase insert domain protein receptor (KDR, f...Figure 18.5 Focal segmental glomerular sclerosis (FSGS), SAND model, 36 expe...Figure 18.6 Focal segmental glomerular sclerosis (FSGS), SAND model, 36 week...Figure 18.7 Proliferative glomerulonephritis. Increased cellularity of glome...Figure 18.8 Membranous glomerulonephritis. Thickened glomerular capillary ba...Figure 18.9 Membranoproliferative glomerulonephritis. Increased cellularity ...Figure 18.10 Sclerotic glomerulus. PAS stain shows positive material in mesa...Figure 18.11 Amyloid. Hyaline material throughout the glomerulus, adhesions ...Figure 18.12 Amyloid. Congo Red stain reveals amyloid. Aged C57BL/6J mouse....Figure 18.13 Collagenopathy. Note abundant eosinophilic material in glomerul...Figure 18.14 Collagenopathy. Note abundant collagen (blue) in glomeruli. Mas...Figure 18.15 Immune‐mediated glomerulonephritis. Human kappa light cha...Figure 18.16 Fibronectin glomerulopathy. Increased focal and diffuse mesangi...Figure 18.17 Tumor lysis syndrome. Blue material is DNA from a necrotic T‐ce...Figure 18.18 Tumor metastases within glomerulus. Metastatic CD3+ (CD3E) lymp...Figure 18.19 Tumor metastases within glomerulus. Histiocytic sarcoma cells w...Figure 18.20 Lupus glomerulonephritis. IgG (green) and C3 (red) fluorescence...Figure 18.21 Polycystic kidney. Note numerous dilated and cystic tubules occ...Figure 18.22 Glycogen storage disease. There is abundant glycogen in tubular...Figure 18.23 Chapparvovirus (MKPV, mouse kidney parvovirus) infection. Many ...Figure 18.24 Streptozocin‐induced clear intranuclear tubule cell inclusions...Figure 18.25 Preneoplastic renal tubule cell atypical hyperplasia. A single ...Figure 18.27 Renal papillary tubular adenoma. There is compression of adjace...Figure 18.28 Solid renal tubular cell adenocarcinoma. Necrosis is seen. Chem...Figure 18.29 Renal clear cell carcinoma. Glycogen‐like clear cytoplasm. Chem...Figure 18.30 Bladder fixation and trimming protocol. Inflate bladder with 50...Figure 18.31 Bladder diffuse and nodular hyperplasia. Note diffuse and nodul...Figure 18.32 Large and small bladder papillomas. The adjacent epithelium is ...Figure 18.33 Bladder transitional cell carcinoma. Invasion of the bladder wa...

19 Chapter 19Figure 19.1 Mouse reproductive tract. (a) Mouse reproductive tract in situ. ...Figure 19.2 Protocol for longitudinal and cross sections of uterine tissue. ...Figure 19.3 Cystic and hemorrhagic ovaries from Esr1−/−‐Rosa26...Figure 19.4 Hypoplastic uterus from an Esr1tm3.1Ksk/Esr1tm3.1Ksk mouse. (a) ...Figure 19.5 Mouse high‐grade serous carcinoma arising from the ovarian surfa...Figure 19.6 Mouse high‐grade serous carcinoma arising from the tubal epithel...Figure 19.7 Mouse serous endometrial carcinoma. (a) Early atypical lesions 6...Figure 19.8 Spontaneous granulosa cell tumor in an aged FVB/NJ mouse (a and ...Figure 19.9 Spontaneous ovarian cysts in an aged C57L/J mouse (a and b). Cys...Figure 19.10 Spontaneous luteoma in the ovary of an aged 129S1/SvlmJ mouse (...

20 Chapter 20Figure 20.1 Mouse male reproductive system. Seminal vesicles (SV), preputial...Figure 20.2 Mouse prostate and associated accessory sex glands en bloc. Semi...Figure 20.3 The mouse preputial glands are composed of acini (A) and large, ...Figure 20.4 The Bulbourethral glands (Cowper’s glands) are multilobular glan...Figure 20.5 Ampullary glands are lined by a cuboidal epithelium with charact...Figure 20.6 The Seminal vesicles are composed of tall columnar epithelium (E...Figure 20.7 Benign polyp of the seminal vesicles in the TRAMP (Tg(TRAMP)8247...Figure 20.8 Gross prostate lobes and Seminal vesicles. (a) Ventral view, (b)...Figure 20.9 The four mouse prostate lobes are histologically distinct. (a) C...Figure 20.10 Classification of lesions of the prostate in genetically engine...Figure 20.11 TRAMP (Tg(TRAMP)8247Ng) mouse model with neuroendocrine carcino...Figure 20.12 Prostatic adenocarcinoma from a mouse with conditional prostate...Figure 20.13 Adenocarcinoma from an overexpressing MYC (FVB‐Tg(ARR2/Pbsn‐MYC...Figure 20.14 Neuroendocrine carcinoma metastasis to the liver from TRAMP mod...Figure 20.15 Testis. (a) Normal seminiferous tubules (arrowheads) separated ...Figure 20.16 Testis. Multinucleate germ cells (symplasts). Symplasts (arrows...Figure 20.17 Testis. Straight seminiferous tubules (tubuli recti) are lined ...Figure 20.18 Epididymis. (A) The head of the epididymis has small lumen line...Figure 20.19 Epididymis, Epithelium with focal karyomegaly. An atypical enla...Figure 20.20 Testis. (a) Tubular necrosis. (b) A higher magnification of ins...Figure 20.21 Epididymis, tail. Dilation, sperm stasis, and granuloma. (a) Se...Figure 20.22 (a) Epididymis‐segmental dilation (arrows) with luminal aggrega...Figure 20.23 Epididymis, body. Epithelial vacuolation. This finding was not ...Figure 20.24 Testis. Diffuse tubular atrophy/hypoplasia. (a) Complete germ c...Figure 20.25 Testis. Multifocal tubular atrophy/hypoplasia, multifocal. (a) ...Figure 20.26 Testis. Failure of meiosis. Seminiferous tubules show spermatoc...Figure 20.27 Testis, Defects in spermiogenesis and spermiation. (a) Defect i...Figure 20.28 Testis. Degeneration of elongated spermatids. Large structures ...Figure 20.29 Testis. Tubular degeneration/atrophy with multinucleate germ ce...Figure 20.30 Testis. Germ cell dissociation. (a) Germ cells are dissociated ...Figure 20.31 Mouse testis. Teratoma. (a) Differentiation into epithelial, me...

21 Chapter 21Figure 21.1 Dorsal view of brain.Figure 21.2 Ventral view of brain.Figure 21.3 Coronal (cross) section of brain at the level of the thalamus, w...Figure 21.4 Coronal (cross) section of brain at the level of the midbrain, w...Figure 21.5 Artifactual vacuolation of the white matter of the cerebellum fo...Figure 21.6 Artifactual spaces surrounding the vessels following intravascul...Figure 21.7 Parasagittal (lateral of midline) section of brain. Nissl stain....Figure 21.8 Sagittal section of spine, showing the orientation of the spinal...Figure 21.9 Cross section of the spinal cord in situ with nerves and ganglia...Figure 21.10 Cross section of spinal cord in situ in an aged C57BL/6 mouse w...Figure 21.11 Dark neuron artifact in mouse cerebrum. HE.Figure 21.12 Touch artifact at the surface of the mouse cerebrum due to hand...Figure 21.13 Hypereosinophilic, dead neurons in the cerebrum of an FVB mouse...Figure 21.14 Artifactual clear space (halos) surrounding oligodendrocytes in...Figure 21.15 Artifactual clear space (perivascular clefts) surrounding blood...Figure 21.16 Artifactual clear space and separation of the dentate gyrus of ...Figure 21.17 Histologic appearance of the normal corpus callosum in a BALB/c...Figure 21.19 Dermoid cyst in the spinal cord of a B6SJL‐Tg(SOD1*G93A)1Gur/J ...Figure 21.20 Encephalitis and abscesses in an immunosuppressed Myd88tm1Aki m...Figure 21.21 Eosinophilic intracytoplasmic neuronal inclusions in the thalam...Figure 21.22 Neuroaxonal dystrophy in the medulla oblongata (gracilis nucleu...Figure 21.23 Neoplastic lymphocytes (lymphoma) expanding the meninges of an ...Figure 21.24 Neuronal loss with astrogliosis in a mouse with a conditional n...Figure 21.25 Ubiquitin positive plaques in the cortex of a seven‐month‐old f...Figure 21.26 Amyloid beta positive plaques in the cortex of a seven‐month‐ol...Figure 21.27 Amyloid plaques and microgliosis in the cortex of a six‐month‐o...Figure 21.28 Tauopathy and neurofibrillary tangles in the medulla oblongata ...Figure 21.29 Constitutive tyrosine hydroxylase expression in the substantia ...Figure 21.30 Neurodegenerative changes with Lewy body‐like inclusions in the...Figure 21.31 Inflammation and demyelination in the spinal cord of a mouse mo...Figure 21.32 Neurons with accumulated intracytoplasmic vacuolated material i...Figure 21.33 Medulloblastoma at the level of the medulla and cerebellum. Ins...

22 Chapter 22Figure 22.1 Age‐matched E13.5 littermates, in which the mouse on the right h...Figure 22.2 Histologic section of affected E13.5 embryo in Figure 22.1, whic...Figure 22.3 Phthisis bulbi resulting from a chronic, severe uveitis in a C57...Figure 22.4 Phthisis bulbi resulting from the compression of the globe by an...Figure 22.5 Corneal opacity in a C57BL/6 mouse arising from keratoconjunctiv...Figure 22.6 Healing corneal ulceration in a C57BL/6 mouse. Superficially the...Figure 22.7 Ocular melanosis in the eye of a C57BL/6 mouse with no notable f...Figure 22.8 Pigment‐associated glaucoma in an aged C57BL/6 mouse. There is a...Figure 22.9 Retinal degeneration in a Swiss Webster outbred model from the R...Figure 22.10 Retinal dysplasia. There is disorderly differentiation, blendin...Figure 22.11 Coronal sections of mouse head. (a) Low magnification view show...Figure 22.12 Failure of mesenchymal condensation and development of superior...Figure 22.13 Otitis media in mouse with a lysosomal storage disease. (a) Mid...Figure 22.14 Lesions of the organ of Corti. Arrows indicate outer hair cells...Figure 22.15 Deafness phenotype in mouse lacking vesicular glutamate transpo...Figure 22.16 Decreased to absent otoconia over the macula (M). (a) Normal ap...

23 Chapter 23Figure 23.1 Mouse bone. (a) Enzyme histochemistry showing TRAP‐positive oste...Figure 23.2 Mouse sternebrae. (a) Wild‐type C57BL/6 mouse showing typical tr...Figure 23.3 Mouse bone – renal osteodystrophy. Increased numbers of os...Figure 23.4 Mouse turbinate. (a) Proliferating cells in bones of ascorbate‐d...Figure 23.5 Mouse femur. Healing fracture in ascorbate‐deficient mouse.Figure 23.6 Mouse kidney (a) and lung (b). Ectopic mineralization.Figure 23.7 Mouse sternum. (a) Cortical and trabecular bone are disorganized...Figure 23.8 Mouse femorotibial joint. (a) Wild‐type bone stained with Alcian...Figure 23.9 Mouse incisor tooth – Amelogenesis imperfecta. (a) Disorga...Figure 23.10 Mouse molar teeth – Dentinogenesis imperfecta. (a) Parall...Figure 23.11 Aged mouse incisor. Deep clefting of enamel layer, intrapulpal ...

Pathology of Genetically Engineered and Other Mutant Mice

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