mortality/aging
• 100% of mutants die within 11 days of exposure to gamma-irradiation compared to 20% of wild-type littermates
• irradiation induced more chromosomal breaks in mutants than in wild-type littermates
|
cellular
• in a model of hypoxia driven tumor neovascularization, endothelial cell apoptosis is increased
|
• spermatocytes are arrested at the pachytene stage of meiosis I in mutants
|
• mouse embryo fibroblasts proliferate poorly in vitro with a marked increase in chromatid breaks
(J:76360)
• primary lung epithelial cells display reduced growth factor stimulated proliferation under hypoxic conditions compared to wild-type control cells
(J:149487)
|
• in a model of hypoxia driven tumor neovascularization, endothelial cell proliferation is decreased
|
growth/size/body
• mutants are smaller than wild-type mice
|
immune system
• switching is impaired
(J:120658)
• however, class switching recombination (CSR)-induced Smu internal deletion, switching region accessibility and switching recombination junctions are normal
(J:120658)
• impaired but partially rescued by short hairpin RNA inhibition of Rbbp8 and enhanced by treatment with the WRNi helicase inhibitor or to a lesser extent the ATM inhibitor Ku55933
(J:194603)
|
• a 50% reduction in the number of B cells is seen without any specific block in development
• an immunoglobin heavy chain class-switch recombination defect is the major cause of the decrease in expression of secondary isotypes of B cells in mutants
|
• a 50% reduction in the number of T cells is seen without any specific block in development
|
• impaired region specific DNA recombination involved in switching immunoglobin heavy chain constant regions results in a 50 - 86% reduction in surface IgG1
|
reproductive system
• spermatocytes are arrested at the pachytene stage of meiosis I in mutants
|
• the diameter of the seminiferous tubules is reduced in mutants compared to wild-type mice
|
small testis
(
J:76360
)
• at 2 months mutant testes are half the size of wild-type testes
|
cardiovascular system
• neovascularization is impaired compared to wild-type controls following induced hind limb ischemia
|
• neovascularization is impaired compared to wild-type controls following induced hind limb ischemia
|
• vascularization of implanted tumors is reduced compared to controls
|
• in a model of hypoxia driven tumor neovascularization, endothelial cell apoptosis is increased
|
• in a model of hypoxia driven tumor neovascularization, endothelial cell proliferation is decreased
|
neoplasm
• vascularization of implanted tumors is reduced compared to controls
|
• both the growth and final weight of implanted Lewis lung carcinomas are reduced compared to controls
|
hematopoietic system
• switching is impaired
(J:120658)
• however, class switching recombination (CSR)-induced Smu internal deletion, switching region accessibility and switching recombination junctions are normal
(J:120658)
• impaired but partially rescued by short hairpin RNA inhibition of Rbbp8 and enhanced by treatment with the WRNi helicase inhibitor or to a lesser extent the ATM inhibitor Ku55933
(J:194603)
|
• a 50% reduction in the number of B cells is seen without any specific block in development
• an immunoglobin heavy chain class-switch recombination defect is the major cause of the decrease in expression of secondary isotypes of B cells in mutants
|
• a 50% reduction in the number of T cells is seen without any specific block in development
|
• impaired region specific DNA recombination involved in switching immunoglobin heavy chain constant regions results in a 50 - 86% reduction in surface IgG1
|
endocrine/exocrine glands
• the diameter of the seminiferous tubules is reduced in mutants compared to wild-type mice
|
small testis
(
J:76360
)
• at 2 months mutant testes are half the size of wild-type testes
|
vision/eye
• neovascularization is impaired compared to wild-type controls following induced hind limb ischemia
|
homeostasis/metabolism
• 100% of mutants die within 11 days of exposure to gamma-irradiation compared to 20% of wild-type littermates
• irradiation induced more chromosomal breaks in mutants than in wild-type littermates
|