Mouse Genome Informatics
hm1
    Mertktm1Grl/Mertktm1Grl
involves: 129P2/OlaHsd
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
reproductive system
(J:142166)
• mutant Sertoli cells show a 35% decrease in phagocytosis of apoptotic spermatogenic cells relative to wild-type controls, as determined by lipid droplet formation using Oil Red O staining (J:133455)

vision/eye
• outer segment tips of the retina are aberrantly extended into the RPE cell layer at P17 such that by P21, there is a 33% increase in overall outer segment length relative to wild-type
• by P35, the outer segment layer becomes very disordered compared to wild-type
• by 2 months of age, nearly all photoreceptors die by apoptosis
• retinal pigment epithelial cells are unable to phagocytose the distal ends of the photoreceptor outer segments

nervous system
• outer segment tips of the retina are aberrantly extended into the RPE cell layer at P17 such that by P21, there is a 33% increase in overall outer segment length relative to wild-type
• by P35, the outer segment layer becomes very disordered compared to wild-type
• by 2 months of age, nearly all photoreceptors die by apoptosis

hematopoietic system
• 2-fold increase in spleen size

cardiovascular system
N
• mice exhibit normal vascular permeability in the liver (J:198769)

immune system
• 2-fold increase in spleen size

pigmentation
• retinal pigment epithelial cells are unable to phagocytose the distal ends of the photoreceptor outer segments


Mouse Genome Informatics
cx2
    Mertktm1Grl/Mertktm1Grl
Tyro3tm1Grl/Tyro3tm1Grl

involves: 129S1/Sv * 129X1/SvJ
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
endocrine/exocrine glands
(J:54681)

reproductive system
(J:54681)
• 3.7% of females exhibit vaginal atresia (J:142166)
• reduced amount of mature sperm in the epididymis (J:54681)
• double mutant Sertoli cells show a ~35% decrease in phagocytosis of apoptotic spermatogenic cells relative to wild-type controls, as determined by lipid droplet formation using Oil Red O staining; this reduction is similar to that observed in Mertktm1Grl singly mutant Sertoli cells (J:133455)


Mouse Genome Informatics
cx3
    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
• endometrial glands are significantly reduced in females with vaginal atresia (J:142166)
• 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


Mouse Genome Informatics
cx4
    Axltm1Grl/Axltm1Grl
Mertktm1Grl/Mertktm1Grl

involves: C57BL/6J
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
immune system

reproductive system
• 4% of females exhibit vaginal atresia (J:142166)
• double mutant Sertoli cells show a ~35% decrease in phagocytosis of apoptotic spermatogenic cells relative to wild-type controls, as determined by lipid droplet formation using Oil Red O staining; this reduction is similar to that observed in Mertktm1Grl singly mutant Sertoli cells (J:133455)