All Phenotypes Xrcc4<tm1Fwa> MGI Mouse

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Phenotypes associated with this allele

Allele Symbol
Allele Name
Allele ID

Xrcc4^tm1Fwa
targeted mutation 1, Frederick W Alt
MGI:1926771

Summary

10 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Xrcc4^tm1Fwa/Xrcc4^tm1Fwa	involves: 129P2/OlaHsd	MGI:3809933
hm2	Xrcc4^tm1Fwa/Xrcc4^tm1Fwa	involves: 129P2/OlaHsd * C57BL/6	MGI:2174810
cn3	Tg(Cr2-cre)3Cgn/? Xrcc4^tm1Fwa/Xrcc4^tm2Fwa	involves: 129P2/OlaHsd * 129S6/SvEvTac	MGI:4352685
cn4	Rag2^tm1Cgn/Rag2^tm1Cgn Xrcc4^tm1Fwa/Xrcc4^tm2Fwa Tg(Cr2-cre)3Cgn/?	involves: 129P2/OlaHsd * 129S6/SvEvTac * C57BL/6	MGI:4352688
cn5	Aicda^tm1Hon/Aicda^tm1Hon Tg(Cr2-cre)3Cgn/? Xrcc4^tm1Fwa/Xrcc4^tm2Fwa	involves: 129P2/OlaHsd * 129S6/SvEvTac * C57BL/6 * CBA	MGI:4352686
cx6	Trp53^tm3.1Holl/Trp53^tm3.1Holl Xrcc4^tm1Fwa/Xrcc4^tm1Fwa	involves: 129P2/OlaHsd	MGI:5465278
cx7	Trp53^tm1Tyj/Trp53^tm1Tyj Xrcc4^tm1Fwa/Xrcc4^tm1Fwa	involves: 129P2/OlaHsd * 129S2/SvPas	MGI:2653516
cx8	Igh^tm2Cgn/Igh^tm2Cgn Igk^tm1Rsky/Igk^tm1Rsky Trp53^tm1Tyj/Trp53^tm1Tyj Xrcc4^tm1Fwa/Xrcc4^tm1Fwa	involves: 129P2/OlaHsd * 129S2/SvPas * 129S6/SvEvTac	MGI:4437907
cx9	Trp53^tm1Xu/Trp53^tm1Xu Xrcc4^tm1Fwa/Xrcc4^tm1Fwa	involves: 129P2/OlaHsd * 129S4/SvJae	MGI:3630331
cx10	Trp53^tm2Xu/Trp53^tm2Xu Xrcc4^tm1Fwa/Xrcc4^tm1Fwa	involves: 129P2/OlaHsd * 129S6/SvEvTac	MGI:3630332

Allelic Composition	Xrcc4^tm1Fwa/Xrcc4^tm1Fwa
Genetic Background	involves: 129P2/OlaHsd

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Xrcc4^tm1Fwa mutation (0 available); any Xrcc4 mutation (26 available)

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

cellular

abnormal cell physiology ( J:110848 )

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

increased cellular sensitivity to gamma-irradiation ( J:120145 )

• ES cells are very sensitive to irradiation as determined by colony survival assay with greater than 10-fold less survival at a dose of 400 rads

increased neuron apoptosis ( J:110848 )

abnormal DNA repair ( J:120145 )

• 18 hours after 80 Gy of gamma-irradiation, significant amounts of genomic DNA leak out of these ES cells during pulse-field electrophoresis while wild-type ES cells are able retain their genomic material

spontaneous chromosome breakage ( J:120145 )

• untreated ES cells have a high incidence of chromosomal breaks and translocations

• almost 15% of cells exhibit abnormal metaphases with most of these abnormalities resulting from chromosome breaks

• the incidence of chromosome breakages is significantly higher than in wild-type ES cells and is twice that of Nhej1^tm1Fwa homozygotes

homeostasis/metabolism

abnormal DNA repair ( J:120145 )

nervous system

increased neuron apoptosis ( J:110848 )

thin cerebral cortex ( J:110848 )

Allelic Composition	Xrcc4^tm1Fwa/Xrcc4^tm1Fwa
Genetic Background	involves: 129P2/OlaHsd * C57BL/6

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Xrcc4^tm1Fwa mutation (0 available); any Xrcc4 mutation (26 available)

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

mortality/aging

lethality throughout fetal growth and development, complete penetrance ( J:65218 )

• dead embryos are first detected at E14.5, becoming more frequent at E1.5-16.5; no live homozygotes have been found at birth

growth/size/body

fetal growth retardation ( J:65218 )

• significantly runted by E15.5 (30% smaller by weight)

immune system

thymus hypoplasia ( J:65218 )

• thymi are significantly smaller than those in wild-type littermates

• total thymocyte numbers are reduced 10-fold compared to controls

nervous system

abnormal cerebral cortex morphology ( J:65218 )

• peak apoptotic cell death is observed in the cerebral cortices at E13-14

• cortical plate remains thin

hematopoietic system

thymus hypoplasia ( J:65218 )

• thymi are significantly smaller than those in wild-type littermates

• total thymocyte numbers are reduced 10-fold compared to controls

endocrine/exocrine glands

thymus hypoplasia ( J:65218 )

• thymi are significantly smaller than those in wild-type littermates

• total thymocyte numbers are reduced 10-fold compared to controls

Allelic Composition	Tg(Cr2-cre)3Cgn/? Xrcc4^tm1Fwa/Xrcc4^tm2Fwa
Genetic Background	involves: 129P2/OlaHsd * 129S6/SvEvTac

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Tg(Cr2-cre)3Cgn mutation (2 available)
Xrcc4^tm1Fwa mutation (0 available); any Xrcc4 mutation (26 available)
Xrcc4^tm2Fwa mutation (0 available); any Xrcc4 mutation (26 available)

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

cellular

spontaneous chromosome breakage ( J:150339 )

• genomic stability is disrupted in activated B cells with chromosome breakage occurring in close to half of cells

• B cells undergoing class switch recombination have even greater increased risk of chromosome breakage due to aberrations at the Igh locus

• there is also increased breakage at the Igk and Igl loci with 1% of stimulated B cells demonstrating this

• Igl breaks in activated B cells are frequently fused to AID-dependent Igh breaks in the same cell to form chromosome 12/16 translocations

• there is also a five-fold increase in Igh-Myc translocations activated B cells compared to controls

hematopoietic system

abnormal class switch recombination ( J:150339 )

• class switch recombination often leads to chromosome breakage at the Igh locus

immune system

abnormal class switch recombination ( J:150339 )

• class switch recombination often leads to chromosome breakage at the Igh locus

Allelic Composition	Rag2^tm1Cgn/Rag2^tm1Cgn Xrcc4^tm1Fwa/Xrcc4^tm2Fwa Tg(Cr2-cre)3Cgn/?
Genetic Background	involves: 129P2/OlaHsd * 129S6/SvEvTac * C57BL/6

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Rag2^tm1Cgn mutation (2 available); any Rag2 mutation (119 available)
Tg(Cr2-cre)3Cgn mutation (2 available)
Xrcc4^tm1Fwa mutation (0 available); any Xrcc4 mutation (26 available)
Xrcc4^tm2Fwa mutation (0 available); any Xrcc4 mutation (26 available)

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

cellular

spontaneous chromosome breakage ( J:150339 )

• genomic stability is disrupted in activated B cells with chromosome breakage occurring in close to half of cells

• B cells undergoing class switch recombination have even greater increased risk of chromosome breakage due to aberrations at the Igh locus

• there is decreased breakage at Igl locus compared to conditional knockouts on a Rag-sufficient background

hematopoietic system

abnormal class switch recombination ( J:150339 )

• class switch recombination often leads to chromosome breakage at the Igh locus

immune system

abnormal class switch recombination ( J:150339 )

• class switch recombination often leads to chromosome breakage at the Igh locus

Allelic Composition	Aicda^tm1Hon/Aicda^tm1Hon Tg(Cr2-cre)3Cgn/? Xrcc4^tm1Fwa/Xrcc4^tm2Fwa
Genetic Background	involves: 129P2/OlaHsd * 129S6/SvEvTac * C57BL/6 * CBA

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Aicda^tm1Hon mutation (7 available); any Aicda mutation (57 available)
Tg(Cr2-cre)3Cgn mutation (2 available)
Xrcc4^tm1Fwa mutation (0 available); any Xrcc4 mutation (26 available)
Xrcc4^tm2Fwa mutation (0 available); any Xrcc4 mutation (26 available)

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

cellular

spontaneous chromosome breakage ( J:150339 )

• genomic stability is disrupted in activated B cells with chromosome breakage occurring in close to half of cells

• however, there is no increased breakage of the Igh locus compared to wild-type controls

• there is increased breakage at the Igk and Igl loci with 1% of stimulated B cells demonstrating this

Allelic Composition	Trp53^tm3.1Holl/Trp53^tm3.1Holl Xrcc4^tm1Fwa/Xrcc4^tm1Fwa
Genetic Background	involves: 129P2/OlaHsd

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Trp53^tm3.1Holl mutation (0 available); any Trp53 mutation (240 available)
Xrcc4^tm1Fwa mutation (0 available); any Xrcc4 mutation (26 available)

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

mortality/aging

embryonic lethality, complete penetrance ( J:191183 )

• no mice are produced

Allelic Composition	Trp53^tm1Tyj/Trp53^tm1Tyj Xrcc4^tm1Fwa/Xrcc4^tm1Fwa
Genetic Background	involves: 129P2/OlaHsd * 129S2/SvPas

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Trp53^tm1Tyj mutation (12 available); any Trp53 mutation (240 available)
Xrcc4^tm1Fwa mutation (0 available); any Xrcc4 mutation (26 available)

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

mortality/aging

premature death ( J:61973 )

• 3-4 weeks after birth

neoplasm

increased B cell derived lymphoma incidence ( J:61973 )

growth/size/body

postnatal growth retardation ( J:61973 )

hematopoietic system

abnormal lymphopoiesis ( J:61973 )

• impaired lymphocyte development

immune system

abnormal lymphopoiesis ( J:61973 )

• impaired lymphocyte development

Allelic Composition	Igh^tm2Cgn/Igh^tm2Cgn Igk^tm1Rsky/Igk^tm1Rsky Trp53^tm1Tyj/Trp53^tm1Tyj Xrcc4^tm1Fwa/Xrcc4^tm1Fwa
Genetic Background	involves: 129P2/OlaHsd * 129S2/SvPas * 129S6/SvEvTac

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Igh^tm2Cgn mutation (1 available); any Igh mutation (44 available)
Igk^tm1Rsky mutation (1 available); any Igk mutation (26 available)
Trp53^tm1Tyj mutation (12 available); any Trp53 mutation (240 available)
Xrcc4^tm1Fwa mutation (0 available); any Xrcc4 mutation (26 available)

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

immune system

abnormal class switch recombination ( J:126758 )

• class switching to IgG1 is 20% to 50% of wild-type

• class switching to IgG3 is 50% of wild-type

• IgH class switching is reduced compared to in wild-type B cells

cellular

increased cellular sensitivity to ionizing radiation ( J:126758 )

• in cultured B cells

spontaneous chromosome breakage ( J:126758 )

• B cell stimulated with anti-CD40 and IL4 exhibit metaphase chromosome breaks unlike similarly treated wild-type cells

hematopoietic system

abnormal class switch recombination ( J:126758 )

• class switching to IgG1 is 20% to 50% of wild-type

• class switching to IgG3 is 50% of wild-type

• IgH class switching is reduced compared to in wild-type B cells

Allelic Composition	Trp53^tm1Xu/Trp53^tm1Xu Xrcc4^tm1Fwa/Xrcc4^tm1Fwa
Genetic Background	involves: 129P2/OlaHsd * 129S4/SvJae

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Trp53^tm1Xu mutation (0 available); any Trp53 mutation (240 available)
Xrcc4^tm1Fwa mutation (0 available); any Xrcc4 mutation (26 available)

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

mortality/aging

mortality/aging ( J:109354 )

N	• embryonic lethality seen in Xrcc4^tm1Fwa homozygotes is rescued at a low frequency when crossed to a Trp53^tm1Xu mouse

cellular

abnormal apoptosis ( J:109354 )

• Trp53-dependent apoptosis in thymocytes is partially impaired after irradiation

Allelic Composition	Trp53^tm2Xu/Trp53^tm2Xu Xrcc4^tm1Fwa/Xrcc4^tm1Fwa
Genetic Background	involves: 129P2/OlaHsd * 129S6/SvEvTac

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Trp53^tm2Xu mutation (2 available); any Trp53 mutation (240 available)
Xrcc4^tm1Fwa mutation (0 available); any Xrcc4 mutation (26 available)

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

mortality/aging

mortality/aging ( J:109354 )

N	• embryonic lethality seen in Xrcc4^tm1Fwa homozygotes is rescued when crossed to a Trp53^tm2Xu mouse

growth/size/body

decreased body size ( J:109354 )

• mice are runted

reproductive system

testicular atrophy ( J:109354 )

• atrophy is detected with age

skeleton

kyphoscoliosis ( J:109354 )

• mice develop acute curvature of the spine as they age

neoplasm

abnormal tumor incidence ( J:109354 )

• double knockouts rarely develop tumors (only 2/34 develop thymic tumors at 93 and 128 days of age) compared with Trp53^tm2Xu homozygotes

integument

thin skin ( J:109354 )

• skin thickness is reduced with age

endocrine/exocrine glands

testicular atrophy ( J:109354 )

• atrophy is detected with age

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