Phenotypes associated with this allele

• Allele Symbol: Xrcc6^tm1Fwa
• Allele Name: targeted mutation 1, Frederick W Alt
• Allele ID: MGI:2179954
• Summary: 3 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Xrcc6^tm1Fwa/Xrcc6^tm1Fwa	involves: 129S6/SvEvTac	MGI:5013918
hm2	Xrcc6^tm1Fwa/Xrcc6^tm1Fwa	involves: 129S6/SvEvTac * C57BL/6J	MGI:3641421
cx3	Igh^tm2Cgn/Igh^+ Xrcc6^tm1Fwa/Xrcc6^tm1Fwa	involves: 129P2/OlaHsd * 129S6/SvEvTac * C57BL/6	MGI:3769719

Genotype
MGI:5013918

hm1

• Allelic Composition: Xrcc6^tm1Fwa/Xrcc6^tm1Fwa
• Genetic Background: involves: 129S6/SvEvTac

• ♀: phenotype observed in females
• ♂: phenotype observed in males
• N: normal phenotype

nervous system

nervous system phenotype ( J:110848 )

N • adult mice exhibit normal nervous system function

N • cerebellar development is normal

increased neuron apoptosis ( J:110848 )

• 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 Lig4^tm1Fwa

• apoptotic cells are localized within or superficial to the ventricular zone

• neuron apoptosis coincides with embryonic neurogenesis

abnormal brainstem morphology ( J:110848 )

• cavities at variable frequency and less severe than in Lig4^tm1Fwa

abnormal striatum morphology ( J:110848 )

• cavities at variable frequency and less severe than in Lig4^tm1Fwa

abnormal diencephalon morphology ( J:110848 )

• cavities at variable frequency and less severe than in Lig4^tm1Fwa

cellular

abnormal cell physiology ( J:110848 )

• mouse embryonic fibroblasts exhibit leakiness of residual end joining in a transient V(D)J recombination end joining assay compared with wild-type cells

increased neuron apoptosis ( J:110848 )

• 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 Lig4^tm1Fwa

• apoptotic cells are localized within or superficial to the ventricular zone

• neuron apoptosis coincides with embryonic neurogenesis

Genotype
MGI:3641421

hm2

• Allelic Composition: Xrcc6^tm1Fwa/Xrcc6^tm1Fwa
• Genetic Background: involves: 129S6/SvEvTac * C57BL/6J

growth/size/body

decreased body size ( J:44361 )

• animals are significantly smaller than controls, but they are viable and fertile

• organ weights are proportional to body weight

slow postnatal weight gain ( J:44361 )

• mice weigh 50-60% that of controls at all ages tested

cellular

abnormal cell physiology ( J:44361 )

• 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

increased cellular sensitivity to gamma-irradiation ( J:44361 )

• 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

decreased cell proliferation ( J:44361 )

• 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

early cellular replicative senescence ( J:44361 )

• the growth rate of mutant MEFs is lower than controls, especially at later passages

• mutant MEFs stop growing earlier than control MEFs

immune system

increased T cell derived lymphoma incidence ( J:44361 )

• 6 of 40 mice (aged 2-7 months) developed thymic tumors; two of these tumors were characterized as CD4+ CD8+ TCRbeta-

abnormal B cell morphology ( J:44361 )

abnormal B cell differentiation ( J:44361 )

• 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

absent immature B cells ( J:44361 )

• no B220+CD43-IgM+ cells are detectable in mutant bone marrow

arrested B cell differentiation ( J:44361 )

• at the pro-B cell stage in mutant mice

absent mature B cells ( J:44361 )

• 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

absent pre-B cells ( J:44361 )

• no B220+CD43-IgM- cells are detectable in mutant bone marrow

abnormal T cell morphology ( J:44361 )

decreased thymocyte number ( J:44361 )

• very few viable thymocytes

abnormal T cell differentiation ( J:44361 )

• 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

increased double-positive T cell number ( J:44361 )

• the thymus from mutant mice usually contain more than 50% double positive lineage cells

decreased single-positive T cell number ( J:44361 )

• CD4+ and CD8+ cells are both detectable but at about 100-fold lower levels than controls

decreased IgM level ( J:44361 )

• no detectable serum IgM

neoplasm

increased T cell derived lymphoma incidence ( J:44361 )

• 6 of 40 mice (aged 2-7 months) developed thymic tumors; two of these tumors were characterized as CD4+ CD8+ TCRbeta-

behavior/neurological

abnormal nursing ( J:44361 )

♀ • females are unable to nurse their newborns and pups require a foster mother for survival

hematopoietic system

increased T cell derived lymphoma incidence ( J:44361 )

• 6 of 40 mice (aged 2-7 months) developed thymic tumors; two of these tumors were characterized as CD4+ CD8+ TCRbeta-

abnormal B cell morphology ( J:44361 )

abnormal B cell differentiation ( J:44361 )

• 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

absent immature B cells ( J:44361 )

• no B220+CD43-IgM+ cells are detectable in mutant bone marrow

arrested B cell differentiation ( J:44361 )

• at the pro-B cell stage in mutant mice

absent mature B cells ( J:44361 )

• 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

absent pre-B cells ( J:44361 )

• no B220+CD43-IgM- cells are detectable in mutant bone marrow

abnormal T cell morphology ( J:44361 )

decreased thymocyte number ( J:44361 )

• very few viable thymocytes

abnormal T cell differentiation ( J:44361 )

• 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

increased double-positive T cell number ( J:44361 )

• the thymus from mutant mice usually contain more than 50% double positive lineage cells

decreased single-positive T cell number ( J:44361 )

• CD4+ and CD8+ cells are both detectable but at about 100-fold lower levels than controls

decreased IgM level ( J:44361 )

• no detectable serum IgM

endocrine/exocrine glands

decreased thymocyte number ( J:44361 )

• very few viable thymocytes

increased T cell derived lymphoma incidence ( J:44361 )

• 6 of 40 mice (aged 2-7 months) developed thymic tumors; two of these tumors were characterized as CD4+ CD8+ TCRbeta-

Genotype
MGI:3769719

cx3

• Allelic Composition: Igh^tm2Cgn/Igh⁺; Xrcc6^tm1Fwa/Xrcc6^tm1Fwa
• Genetic Background: involves: 129P2/OlaHsd * 129S6/SvEvTac * C57BL/6

immune system

abnormal B cell differentiation ( J:44361 )

• mice carrying a rearranged IgH (heavy chain) variable region from a B1-8 clone and homozygous for Xrcc6^tm1Fwa 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"

hematopoietic system

abnormal B cell differentiation ( J:44361 )

• mice carrying a rearranged IgH (heavy chain) variable region from a B1-8 clone and homozygous for Xrcc6^tm1Fwa 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"