Mouse Genome Informatics
cx
    Axltm1Grl/Axltm1Grl
Mertktm1Grl/Mertktm1Grl
Tyro3tm1Grl/Tyro3tm1Grl

involves: 129S1/Sv * 129X1/SvJ * C57BL/6J
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
       
cardiovascular system
• increased apoptosis and cellular degeneration in vessel walls
• hemorrhage is observed in several tissues, including the brain, and is associated with autoimmunity

cellular
• an increase in apoptosis is observed in the hippocampus, cerebellum, neocortex, the epithelium of the prostate, the granulosa cells of the ovary, the parenchyma of the liver, the walls of blood vessels, and the spleen

endocrine/exocrine glands
• apoptosis of granulosa cells (J:54681)
• the epithelium of the prostate exhibits altered histology, increased apoptosis and cellular degeneration (J:54681)
• cellular organization of the seminiferous tubules is perturbed (J:54681)
• approximately one-third the size of wild-type testes (J:54681)

hematopoietic system
• hyperproliferation of B and T cells, leading to ectopic colonies of lymphocytes in most organs
• B cells are constituitively activated
• T cells are constituitively activated
• populated by apoptotic cells
• spleens grow at an elevated rate compared to wild-type starting at 4 weeks of age, such that at 1 year of age, spleen weight is 10 times that of wild-type (J:70420)
• cultured macrophages produce excessive amounts of IL-12 and exhibit a 3.5-fold increase in generalized phagocytosis

immune system
• hyperproliferation of B and T cells, leading to ectopic colonies of lymphocytes in most organs
• T cells are constituitively activated
• populated by apoptotic cells
• spleens grow at an elevated rate compared to wild-type starting at 4 weeks of age, such that at 1 year of age, spleen weight is 10 times that of wild-type (J:70420)
• serum levels of TNFalpha are more than doubled in mutants 1 hour after LPS injection compared to wild-type
• notable in the submaxillary, popliteal, and mesenteric nodal stations
• chronic hyperactivation of antigen presenting cells
• B cells are constituitively activated
• cultured macrophages produce excessive amounts of IL-12 and exhibit a 3.5-fold increase in generalized phagocytosis
• all mutants develop autoimmunity resulting from chronic hyperactivation of antigen-presenting cells
• mutants exhibit autoantibodies to varous collagens, to phospholipids, cardiolipin, phosphatidylinositol, and phosphatidylethanolamine
• inflammation and lymphocyte invasion of joints is seen at 6 months of age, leading to swollen joints

liver/biliary system
• increased apoptosis and cellular degeneration in parenchyma

reproductive system
• apoptosis of granulosa cells (J:54681)
• the epithelium of the prostate exhibits altered histology, increased apoptosis and cellular degeneration (J:54681)
• cellular organization of the seminiferous tubules is perturbed (J:54681)
• approximately one-third the size of wild-type testes (J:54681)
• uterine wall of females with vaginal atresia is thinner (J:142166)
• endometrial glands are significantly reduced in females with vaginal atresia (J:142166)
• in females with vaginal atresia (J:142166)
• 16% of females exhibit vaginal atresia (J:142166)
• progressive depletion of germ cells; release of the few mature sperm that are produced is delayed beyond the normal stage of release (tubule stage VIII) (J:54681)
• progressive death of differentiating germ cells resulting in an absence of mature sperm (J:54681)
• triple mutant Sertoli cells show a 7.6-fold reduction in phagocytosis of apoptotic spermatogenic cells relative to wild-type controls, as determined by lipid droplet formation using Oil Red O staining (J:133455)
• triple mutant Sertoli cells show a 4-fold reduction in phagocytosis of apoptotic spermatogenic cells relative to Mertktm1Grl singly mutant Sertoli cells (J:133455)
• notably, triple mutant Sertoli cells bind apoptotic spermatogenic cells with an average of 0.8 per Sertoli cell, whereas wild-type and Mertktm1Grl singly mutant Sertoli cells bind to apoptotic germ cells similarly with 2.8 and 2.6 per Sertoli cells, respectively (J:133455)
• however, triple mutant Sertoli cells show normal ingestion of latex beads relative to wild-type Sertoli cells, indicating that the phagocytic deficit is specific to the ingestion of apoptotic spermatogenic cells (J:133455)
(J:54681)
• most females do not carry pregnanices to term (J:70420)
(J:54681)

vision/eye
• mutants are blind due to postnatal degeneration of retinal rods and cones

nervous system
• hippocampus shows altered histology, increased apoptosis, and cellular degeneration
• neocortex shows altered histology, increased apoptosis, and cellular degeneration
• cerebellum exhibits altered histology, increased apoptosis, and cellular degeneration

homeostasis/metabolism
• serum levels of TNFalpha are more than doubled in mutants 1 hour after LPS injection compared to wild-type
• thromboses are seen in several tissues such as the brain and are associated with autoimmunity

skeleton
• inflammation and lymphocyte invasion of joints is seen at 6 months of age, leading to swollen joints

integument
• a manifestation of autoimmunity

Mouse Models of Human Disease
OMIM IDRef(s)
Autoimmune Disease 109100 J:70420