Читать книгу Pathology of Genetically Engineered and Other Mutant Mice - Группа авторов - Страница 13

Naturally occurring and induced changes in genes often result in a specific phenotype at the clinical and histopathological levels. The cause of this phenomenon is that genes have specific functions that play a role in the normal homeostasis of cells, tissues, and organs. A genetically engineered mouse () line represents a tool to investigate the effects resulting from the partial or complete loss of gene function or the gain of normal or abnormal functions. The genes are often found to function in specific cellular organelles and biochemical/molecular pathways important for normal biological functions (Figure 1.1) [10]. Cells involved in common gene functions can be single cell types in single tissues, multiple cells types in a single tissue, or multiple cells types in multiple tissues. Gene expression can also be induced in specific cells and tissues by normal and abnormal body functions, or by exposure to external factors such as drugs, infectious agents, environmental modifications, and ingested foods.

Mutant mice often exhibit histopathological changes (lesions) in tissues and organs that are associated with gene function, but the ultimate clinical phenotype can be influenced by various factors. Much of the histopathology found in mutant mice is in the usual spectrum of degenerative, inflammatory, proliferative, and neoplastic changes also found in nonmutant mice. Nouvelle lesions do occur commonly in some lines of mutant mice. These include unique developmental changes, cellular morphological changes, patterns of lesions, types of proliferative lesions, and often strain specific cancer types. These may be due to specific naturally occurring mutations (polymorphisms) in genes that can serve as genetic based models for disease. Spontaneous mutants made up the bulk of mouse models until the advent first of radiation and then chemical mutagenesis programs. The spectrum of spontaneous lesions is noted in each organ‐specific chapter. Often the lesions are identical or very similar to those associated human genetic disorders, but they also may vary from human lesions. The genetic background of the mice often plays a role in spontaneous as well as induced disease phenotypes.

Figure 1.1 Classes of proteins associated with human genetic diseases.

Source: Nussbaum (2007). Reprinted with permission of Elsevier