Читать книгу Pathology of Genetically Engineered and Other Mutant Mice - Группа авторов - Страница 113

Hematopoiesis refers to the production of erythrocytes, leukocytes, and platelets from hematopoietic stem cells (HSCs), a population of self‐renewing cells that can give rise to all blood cell lineages. HSCs are needed throughout the life of mice to maintain blood cell populations because of their relatively short lifespan. HSCs are found in the bone marrow and spleen of adult mice and can be recruited to other extramedullary tissues when there is increased demand for hematopoiesis.

The hemopoietic system is derived from the mesoderm in three waves during embryonal development. The first and second waves occur in the yolk sac of the embryo beginning at embryonal day (ED) 7, and generate blood cells that supply the developing embryo including macrophages involved in tissue remodeling [1]. The definitive HSCs, which can reconstitute the entire hematopoietic system of a lethally irradiated adult mouse, are generated in the third wave around ED 10.5 from the hemogenic endothelium of the dorsal aorta of the aorta‐gonad‐mesonephros (AGM) tissue. The generation of HSCs is dependent on proinflammatory cytokines secreted by macrophages in the arterial wall and by catecholamines supplied by the sympathetic nervous system in the developing embryo [2, 3]. The HSCs migrate from the AGM to the fetal liver where they undergo marked proliferation between ED 11 and ED 16. Additional HSCs are supplied to the fetal liver by the vitelline and umbilical arteries. From the fetal liver, HSCs move to the fetal spleen from around ED15.5 until a few weeks after birth. Hemopoietic stem cells in the spleen of adult mice are mostly committed to erythropoiesis. In addition, HSCs begin to populate the bone marrow starting at ED17.5. They undergo a rapid expansion in the bone marrow during the first three weeks after birth after which they become quiescent [1].

We describe here the pathology of the hemopoietic and lymphoid tissues with an emphasis on changes in mice with spontaneous and genetically engineered mutations. A detailed review of the pathology of these tissues in mice and rats was recently published as part of the INHAND Project (International Harmonization of Nomenclature and Diagnostic Criteria for Lesions in Rats and Mice) [4].