All Phenotypes Xrcc4<tm2Fwa> MGI Mouse

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Phenotypes associated with this allele

Allele Symbol
Allele Name
Allele ID

Xrcc4^tm2Fwa
targeted mutation 2, Frederick W Alt
MGI:3641440

Summary

6 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
cn1	Tg(Cr2-cre)3Cgn/? Xrcc4^tm1Fwa/Xrcc4^tm2Fwa	involves: 129P2/OlaHsd * 129S6/SvEvTac	MGI:4352685
cn2	Rag2^tm1Cgn/Rag2^tm1Cgn Xrcc4^tm1Fwa/Xrcc4^tm2Fwa Tg(Cr2-cre)3Cgn/?	involves: 129P2/OlaHsd * 129S6/SvEvTac * C57BL/6	MGI:4352688
cn3	Aicda^tm1Hon/Aicda^tm1Hon Tg(Cr2-cre)3Cgn/? Xrcc4^tm1Fwa/Xrcc4^tm2Fwa	involves: 129P2/OlaHsd * 129S6/SvEvTac * C57BL/6 * CBA	MGI:4352686
cn4	Lig4^tm1Fwa/Lig4^tm1Fwa Tg(Cr2-cre)3Cgn/0 Xrcc4^tm2Fwa/Xrcc4^tm2Fwa	involves: 129S6/SvEvTac	MGI:4437909
cn5	Trp53^tm1Brd/Trp53⁺ Xrcc4^tm2.1Fwa/Xrcc4^tm2Fwa Tg(Nes-cre)1Kln/0	involves: 129S6/SvEvTac * 129S7/SvEvBrd * C57BL/6 * SJL	MGI:3652715
cn6	Trp53^tm1Brd/Trp53^tm1Brd Xrcc4^tm2.1Fwa/Xrcc4^tm2Fwa Tg(Nes-cre)1Kln/0	involves: 129S6/SvEvTac * 129S7/SvEvBrd * C57BL/6 * SJL	MGI:3652717

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 (25 available)
Xrcc4^tm2Fwa mutation (0 available); any Xrcc4 mutation (25 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 (117 available)
Tg(Cr2-cre)3Cgn mutation (2 available)
Xrcc4^tm1Fwa mutation (0 available); any Xrcc4 mutation (25 available)
Xrcc4^tm2Fwa mutation (0 available); any Xrcc4 mutation (25 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 (55 available)
Tg(Cr2-cre)3Cgn mutation (2 available)
Xrcc4^tm1Fwa mutation (0 available); any Xrcc4 mutation (25 available)
Xrcc4^tm2Fwa mutation (0 available); any Xrcc4 mutation (25 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	Lig4^tm1Fwa/Lig4^tm1Fwa Tg(Cr2-cre)3Cgn/0 Xrcc4^tm2Fwa/Xrcc4^tm2Fwa
Genetic Background	involves: 129S6/SvEvTac

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Lig4^tm1Fwa mutation (1 available); any Lig4 mutation (44 available)
Tg(Cr2-cre)3Cgn mutation (2 available)
Xrcc4^tm2Fwa mutation (0 available); any Xrcc4 mutation (25 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^tm1Brd/Trp53⁺ Xrcc4^tm2.1Fwa/Xrcc4^tm2Fwa Tg(Nes-cre)1Kln/0
Genetic Background	involves: 129S6/SvEvTac * 129S7/SvEvBrd * C57BL/6 * SJL

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Tg(Nes-cre)1Kln mutation (4 available)
Trp53^tm1Brd mutation (5 available); any Trp53 mutation (232 available)
Xrcc4^tm2.1Fwa mutation (0 available); any Xrcc4 mutation (25 available)
Xrcc4^tm2Fwa mutation (0 available); any Xrcc4 mutation (25 available)

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

mortality/aging

mortality/aging ( J:109585 )

N	• mice survive beyond 16 months

Allelic Composition	Trp53^tm1Brd/Trp53^tm1Brd Xrcc4^tm2.1Fwa/Xrcc4^tm2Fwa Tg(Nes-cre)1Kln/0
Genetic Background	involves: 129S6/SvEvTac * 129S7/SvEvBrd * C57BL/6 * SJL

Find Mice

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

mortality/aging

premature death ( J:109585 )

• mice become moribund between 12 and 14 weeks of age with 20/23 mice dead by 25 weeks

nervous system

increased medulloblastoma incidence ( J:109585 )

• mice develop medulloblastomas

abnormal cerebellar granule layer morphology ( J:109585 )

• mice at 4 and 8.5 weeks of age show multifocal tumor masses expanding from the granular layer

abnormal cerebellum vermis morphology ( J:109585 )

• at 12-14 weeks mice have aggressive medulloblastomas in the vermis or hemisphere

craniofacial

enlarged cranium ( J:109585 )

• at 12-14 weeks skulls of mice show rapid morphological enlargement

skeleton

enlarged cranium ( J:109585 )

• at 12-14 weeks skulls of mice show rapid morphological enlargement

neoplasm

increased medulloblastoma incidence ( J:109585 )

• mice develop medulloblastomas

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
medulloblastoma		DOID:0050902	OMIM:155255	J:109585

Contributing Projects: Mouse Genome Database (MGD), Gene Expression Database (GXD), Mouse Models of Human Cancer database (MMHCdb) (formerly Mouse Tumor Biology (MTB)), Gene Ontology (GO)
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