Phenotypes associated with this allele
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| Find Mice |
Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Xrcc6tm1Fwa mutation
(2 available);
any
Xrcc6 mutation
(61 available)
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nervous system
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• adult mice exhibit normal nervous system function
• cerebellar development is normal
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• at E12.5, mice exhibit increased apoptotic cells in the developing spinal cord, cerebral cortex, diencephalon, midbrain, and hindbrain compared to in wild-type mice
• apoptosis in the cerebral cortex is less severe than in Lig4tm1Fwa
• apoptotic cells are localized within or superficial to the ventricular zone
• neuron apoptosis coincides with embryonic neurogenesis
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• cavities at variable frequency and less severe than in Lig4tm1Fwa
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• cavities at variable frequency and less severe than in Lig4tm1Fwa
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• cavities at variable frequency and less severe than in Lig4tm1Fwa
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cellular
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• mouse embryonic fibroblasts exhibit leakiness of residual end joining in a transient V(D)J recombination end joining assay compared with wild-type cells
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• at E12.5, mice exhibit increased apoptotic cells in the developing spinal cord, cerebral cortex, diencephalon, midbrain, and hindbrain compared to in wild-type mice
• apoptosis in the cerebral cortex is less severe than in Lig4tm1Fwa
• apoptotic cells are localized within or superficial to the ventricular zone
• neuron apoptosis coincides with embryonic neurogenesis
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| Find Mice |
Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Xrcc6tm1Fwa mutation
(2 available);
any
Xrcc6 mutation
(61 available)
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growth/size/body
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• animals are significantly smaller than controls, but they are viable and fertile
• organ weights are proportional to body weight
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• mice weigh 50-60% that of controls at all ages tested
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cellular
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• in Rag1 and Rag2 transfected mutant MEFs, recovery of plasmids harboring recombination signal sequence (RS) joins is reduced by 10 to 20-fold, while that of plasmids harboring coding joins is reduced by 200-fold
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• in MEF populations sychronized by serum starvation, gamma-irradiation at G1 and G2/M resulted in permanant arrest of cells whereas control cells recovered by resuming the cell cycle
• in asynchronus populations, gamma- irradiated mutant MEFs arrest at G2/M
• homozygous mutant ES cells accumulate at G2/M after exposure to gamma-irradiation prior to apoptosis
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• 40% fewer mutant MEFs are in S phase in asynchronous cell populations compared to controls
• in cells synchronized by serum starvation, both control and mutant cells reentered S phase by 10 hours, but fewer mutant cells are in S phase between 10 and 24 hours; in addition, at 48 hours fewer mutant cells had replicated and many of these were still in G0/G1
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• the growth rate of mutant MEFs is lower than controls, especially at later passages
• mutant MEFs stop growing earlier than control MEFs
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immune system
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• both D-J and V-DJ rearrangements are detectable in mutant bone marrow DNA but are greatly reduced (more than 100-fold) in level compared to controls, so functional Ig rearrangements can be generated at low frequency
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• no B220+CD43-IgM+ cells are detectable in mutant bone marrow
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• at the pro-B cell stage in mutant mice
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• in spleens of mutant mice aged 3-18 weeks, no mature B220+IgM+ B lineage cells are detected
• no B lineage cells are detected in the peritoneal cavity of mutant mice
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• no B220+CD43-IgM- cells are detectable in mutant bone marrow
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• very few viable thymocytes
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• T cell differentiation is impaired
• the level of recombination signal sequence (RS) joins in mutant thymocyte DNA is substantially reduced compared to controls and the recovered joins are imprecise
• both Tcrbeta D-J and V-DJ rearrangements are detectable in thymic DNA but are variably reduced in level compared to controls
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• the thymus from mutant mice usually contain more than 50% double positive lineage cells
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• CD4+ and CD8+ cells are both detectable but at about 100-fold lower levels than controls
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• no detectable serum IgM
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neoplasm
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• 6 of 40 mice (aged 2-7 months) developed thymic tumors; two of these tumors were characterized as CD4+ CD8+ TCRbeta-
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behavior/neurological
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• females are unable to nurse their newborns and pups require a foster mother for survival
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hematopoietic system
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• both D-J and V-DJ rearrangements are detectable in mutant bone marrow DNA but are greatly reduced (more than 100-fold) in level compared to controls, so functional Ig rearrangements can be generated at low frequency
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• no B220+CD43-IgM+ cells are detectable in mutant bone marrow
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• at the pro-B cell stage in mutant mice
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• in spleens of mutant mice aged 3-18 weeks, no mature B220+IgM+ B lineage cells are detected
• no B lineage cells are detected in the peritoneal cavity of mutant mice
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• no B220+CD43-IgM- cells are detectable in mutant bone marrow
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• very few viable thymocytes
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• T cell differentiation is impaired
• the level of recombination signal sequence (RS) joins in mutant thymocyte DNA is substantially reduced compared to controls and the recovered joins are imprecise
• both Tcrbeta D-J and V-DJ rearrangements are detectable in thymic DNA but are variably reduced in level compared to controls
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• the thymus from mutant mice usually contain more than 50% double positive lineage cells
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• CD4+ and CD8+ cells are both detectable but at about 100-fold lower levels than controls
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• no detectable serum IgM
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endocrine/exocrine glands
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• very few viable thymocytes
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• 6 of 40 mice (aged 2-7 months) developed thymic tumors; two of these tumors were characterized as CD4+ CD8+ TCRbeta-
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immune system
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• mice carrying a rearranged IgH (heavy chain) variable region from a B1-8 clone and homozygous for Xrcc6tm1Fwa exhibit small but detectable populations of peripheral kappa-light chain expressing IgM+ B cells with functional light chain rearrangements; this indicates that some light chain rearrangment can occur in Xrcc6-deficient mice and the defect in B cell differentiation is "leaky"
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hematopoietic system
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• mice carrying a rearranged IgH (heavy chain) variable region from a B1-8 clone and homozygous for Xrcc6tm1Fwa exhibit small but detectable populations of peripheral kappa-light chain expressing IgM+ B cells with functional light chain rearrangements; this indicates that some light chain rearrangment can occur in Xrcc6-deficient mice and the defect in B cell differentiation is "leaky"
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Analysis Tools