Mouse Genome Informatics
hm1
     Mertktm1Grl/Mertktm1Grl
Not Specified
Key:
♀ phenotype observed in females WTSI Wellcome Trust Sanger Institute
♂ phenotype observed in males Euro Europhenome
N normal phenotype
immune system
enlarged spleen ( J:54681 )
• 2-fold increase in spleen size

vision/eye
abnormal photoreceptor outer segment morphology ( J:116526 )
• 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
disorganized photoreceptor outer segment ( J:116526 )
• by P35, the outer segment layer becomes very disordered compared to wild-type
retinal photoreceptor degeneration ( J:116526 )
• by 2 months of age, nearly all photoreceptors die by apoptosis
abnormal retinal pigment epithelium morphology ( J:116526 )
• retinal pigment epithelial cells are unable to phagocytose the distal ends of the photoreceptor outer segments

nervous system
abnormal photoreceptor outer segment morphology ( J:116526 )
• 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
disorganized photoreceptor outer segment ( J:116526 )
• by P35, the outer segment layer becomes very disordered compared to wild-type
retinal photoreceptor degeneration ( J:116526 )
• by 2 months of age, nearly all photoreceptors die by apoptosis

hematopoietic system
enlarged spleen ( J:54681 )
• 2-fold increase in spleen size

pigmentation
abnormal retinal pigment epithelium morphology ( J:116526 )
• retinal pigment epithelial cells are unable to phagocytose the distal ends of the photoreceptor outer segments

reproductive system
vagina atresia ( J:142166 )
(J:142166)
decreased Sertoli cell phagocytosis ( J:133455 )
• 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)


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 Euro Europhenome
N normal phenotype
endocrine/exocrine glands
small testis ( J:54681 )
(J:54681)

reproductive system
small testis ( J:54681 )
(J:54681)
vagina atresia ( J:142166 )
• 3.7% of females exhibit vaginal atresia (J:142166)
oligozoospermia ( J:54681 )
• reduced amount of mature sperm in the epididymis (J:54681)
decreased Sertoli cell phagocytosis ( J:133455 )
• 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 Euro Europhenome
N normal phenotype
cardiovascular system
abnormal blood vessel morphology ( J:54681 )
• increased apoptosis and cellular degeneration in vessel walls
internal hemorrhage ( J:70420 )
• hemorrhage is observed in several tissues, including the brain, and is associated with autoimmunity

cellular
abnormal apoptosis ( J:54681 )
• 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
abnormal B cell activation ( J:70420 )
• B cells are constituitively activated
abnormal T cell activation ( J:70420 )
• T cells are constituitively activated

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

hematopoietic system
abnormal B cell activation ( J:70420 )
• B cells are constituitively activated
abnormal T cell activation ( J:70420 )
• T cells are constituitively activated
increased lymphocyte cell number ( J:70420 )
• hyperproliferation of B and T cells, leading to ectopic colonies of lymphocytes in most organs
abnormal spleen morphology ( J:54681 )
• populated by apoptotic cells
enlarged spleen ( J:54681 , J:70420 )
• 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)

immune system
abnormal T cell activation ( J:70420 )
• T cells are constituitively activated
increased lymphocyte cell number ( J:70420 )
• hyperproliferation of B and T cells, leading to ectopic colonies of lymphocytes in most organs
abnormal spleen morphology ( J:54681 )
• populated by apoptotic cells
enlarged spleen ( J:54681 , J:70420 )
• 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)
increased circulating tumor necrosis factor level ( J:70420 )
• serum levels of TNFalpha are more than doubled in mutants 1 hour after LPS injection compared to wild-type
enlarged lymph nodes ( J:70420 )
• notable in the submaxillary, popliteal, and mesenteric nodal stations
abnormal professional antigen presenting cell physiology ( J:70420 )
• chronic hyperactivation of antigen presenting cells
abnormal B cell activation ( J:70420 )
• B cells are constituitively activated
abnormal macrophage physiology ( J:70420 )
• cultured macrophages produce excessive amounts of IL-12 and exhibit a 3.5-fold increase in generalized phagocytosis
altered susceptibility to autoimmune disorder ( J:70420 )
• all mutants develop autoimmunity resulting from chronic hyperactivation of antigen-presenting cells
increased autoantibody level ( J:70420 )
• mutants exhibit autoantibodies to varous collagens, to phospholipids, cardiolipin, phosphatidylinositol, and phosphatidylethanolamine
joint inflammation ( J:70420 )
• inflammation and lymphocyte invasion of joints is seen at 6 months of age, leading to swollen joints

liver/biliary system
liver degeneration ( J:54681 )
• increased apoptosis and cellular degeneration in parenchyma

reproductive system
abnormal granulosa cell morphology ( J:54681 )
• apoptosis of granulosa cells (J:54681)
abnormal prostate gland epithelium morphology ( J:54681 )
• the epithelium of the prostate exhibits altered histology, increased apoptosis and cellular degeneration (J:54681)
abnormal seminiferous tubule morphology ( J:54681 )
• cellular organization of the seminiferous tubules is perturbed (J:54681)
small testis ( J:54681 )
• approximately one-third the size of wild-type testes (J:54681)
abnormal uterus morphology ( J:142166 )
• uterine wall of females with vaginal atresia is thinner (J:142166)
decreased endometrial gland number ( J:142166 )
• endometrial glands are significantly reduced in females with vaginal atresia (J:142166)
enlarged uterus ( J:142166 )
• in females with vaginal atresia (J:142166)
vagina atresia ( J:142166 )
• 16% of females exhibit vaginal atresia (J:142166)
abnormal spermatogenesis ( J:54681 )
• 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)
azoospermia ( J:54681 )
• progressive death of differentiating germ cells resulting in an absence of mature sperm (J:54681)
decreased Sertoli cell phagocytosis ( J:133455 )
• 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)
reduced female fertility ( J:54681 , J:70420 )
(J:54681)
• most females do not carry pregnanices to term (J:70420)
male infertility ( J:54681 )
(J:54681)

vision/eye
blindness ( J:54681 )
• mutants are blind due to postnatal degeneration of retinal rods and cones

nervous system
abnormal hippocampus morphology ( J:54681 )
• hippocampus shows altered histology, increased apoptosis, and cellular degeneration
abnormal cerebral cortex morphology ( J:54681 )
• neocortex shows altered histology, increased apoptosis, and cellular degeneration
abnormal cerebellum morphology ( J:54681 )
• cerebellum exhibits altered histology, increased apoptosis, and cellular degeneration

homeostasis/metabolism
increased circulating tumor necrosis factor level ( J:70420 )
• serum levels of TNFalpha are more than doubled in mutants 1 hour after LPS injection compared to wild-type
thrombosis ( J:70420 )
• thromboses are seen in several tissues such as the brain and are associated with autoimmunity

skeleton
joint inflammation ( J:70420 )
• inflammation and lymphocyte invasion of joints is seen at 6 months of age, leading to swollen joints

integument
skin lesions ( J:70420 )
• 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 Euro Europhenome
N normal phenotype
immune system

reproductive system
vagina atresia ( J:142166 )
• 4% of females exhibit vaginal atresia (J:142166)
decreased Sertoli cell phagocytosis ( J:133455 )
• 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)