All Phenotypes Lig4<tm1Fwa> MGI Mouse

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Phenotypes associated with this allele

Allele Symbol
Allele Name
Allele ID

Lig4^tm1Fwa
targeted mutation 1, Frederick W Alt
MGI:1857732

Summary

12 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Lig4^tm1Fwa/Lig4^tm1Fwa	involves: 129S6/SvEvTac	MGI:3839954
hm2	Lig4^tm1Fwa/Lig4^tm1Fwa	involves: 129S6/SvEvTac * C57BL/6	MGI:2182000
ht3	Lig4^tm1Fwa/Lig4⁺	involves: 129S6/SvEvTac * C57BL/6	MGI:3655985
cn4	Lig4^tm1Fwa/Lig4^tm1Fwa Tg(Cr2-cre)3Cgn/0 Xrcc4^tm2Fwa/Xrcc4^tm2Fwa	involves: 129S6/SvEvTac	MGI:4437909
cx5	Igh^tm2Cgn/Igh^tm2Cgn Igk^tm1Rsky/Igk^tm1Rsky Lig4^tm1Fwa/Lig4^tm1Fwa Trp53^tm1Tyj/Trp53^tm1Tyj	involves: 129P2/OlaHsd * 129S2/SvPas * 129S6/SvEvTac	MGI:4437910
cx6	Lig4^tm1Fwa/Lig4^tm1Fwa Trp53^tm1Brd/Trp53⁺	involves: 129S6/SvEvTac * 129S7/SvEvBrd	MGI:3656004
cx7	Lig4^tm1Fwa/Lig4^tm1Fwa Trp53^tm1Brd/Trp53^tm1Brd	involves: 129S6/SvEvTac * 129S7/SvEvBrd	MGI:3656003
cx8	Xrcc5^tm1Dbr/Xrcc5^tm1Dbr Lig4^tm1Fwa/Lig4^tm1Fwa	involves: 129S6/SvEvTac * C57BL/6	MGI:3655986
cx9	Xrcc5^tm1Dbr/Xrcc5⁺ Lig4^tm1Fwa/Lig4⁺	involves: 129S6/SvEvTac * C57BL/6	MGI:3655987
cx10	Paxx^em1Spj/Paxx^em1Spj Lig4^tm1Fwa/Lig4^tm1Fwa	involves: 129S6/SvEvTac * C57BL/6 * C57BL/6NTac	MGI:5829792
cx11	Cdkn2a^tm1Rdp/Cdkn2a⁺ Lig4^tm1Fwa/Lig4^tm1Fwa	involves: 129/Sv * 129S6/SvEvTac * C57BL/6J * SJL	MGI:3656002
cx12	Cdkn2a^tm1Rdp/Cdkn2a^tm1Rdp Lig4^tm1Fwa/Lig4^tm1Fwa	involves: 129/Sv * 129S6/SvEvTac * C57BL/6J * SJL	MGI:3656001

Allelic Composition	Lig4^tm1Fwa/Lig4^tm1Fwa
Genetic Background	involves: 129S6/SvEvTac

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Lig4^tm1Fwa mutation (2 available); any Lig4 mutation (46 available)

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

nervous system

increased forebrain apoptosis ( J:110848 )

• at E12.5, mice exhibit increased apoptotic cells in the developing cerebral cortex and diencephalon compared to in wild-type mice

increased spinal cord apoptosis ( J:110848 )

• at E12.5, mice exhibit increased apoptotic cells in the spinal cord compared to in wild-type mice

abnormal brainstem morphology ( J:110848 )

• large cavities

abnormal striatum morphology ( J:110848 )

• large cavities

abnormal diencephalon morphology ( J:110848 )

• large cavities

thin cerebral cortex ( J:110848 )

• at E12.5, mice exhibit increased apoptotic cells in the developing cerebral cortex compared to in wild-type mice

• apoptosis in the cerebral cortex is more severe than in Xrcc6^tm1Fwa

cellular

abnormal cell physiology ( J:110848 )

• mouse embryonic fibroblasts fail to produce RS joining in a transient V(D)J recombination end joining assay unlike wild-type cells

increased cellular sensitivity to ionizing radiation ( J:147247 )

• cre-treated mouse embryonic fibroblasts exhibit increased cellular sensitivity to ionizing radiation compared to wild-type and Mre11a deficient cells

increased forebrain apoptosis ( J:110848 )

• at E12.5, mice exhibit increased apoptotic cells in the developing cerebral cortex and diencephalon compared to in wild-type mice

increased spinal cord apoptosis ( J:110848 )

• at E12.5, mice exhibit increased apoptotic cells in the spinal cord compared to in wild-type mice

chromosomal instability ( J:147247 )

• mouse embryonic fibroblasts (MEFs) exhibit chromosome fragments with few gaps or breaks within single chromatids

• MEFs exhibit less chromosomal instability than in Mre11a deficient MEFs

• following exposure to gamma radiation, cre-exposed MEFs fail to exhibit a downward trend in frequency of chromosomal anomalies unlike similarly treated wild-type cells

induced chromosome breakage ( J:147247 )

• cre-treated mouse embryonic fibroblasts exhibit hypersensitivity to aphidicolin compared to similarly treated wild-type cells

Allelic Composition	Lig4^tm1Fwa/Lig4^tm1Fwa
Genetic Background	involves: 129S6/SvEvTac * C57BL/6

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Lig4^tm1Fwa mutation (2 available); any Lig4 mutation (46 available)

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

mortality/aging

lethality throughout fetal growth and development, incomplete penetrance ( J:50865 )

• homozygotes are obtained at the expected Mendelian frequency at E15.0-E16.0; however, a significant number of homozygotes are found dead at E16.5-E17.5

prenatal lethality, complete penetrance ( J:80467 )

• no live-born mice Lig4-null mice are generated from Lig4^tm1Fwa/+, Xrcc5^+/+ crosses (0/153 total offspring)

growth/size/body

decreased fetal size ( J:50865 )

• at E13.5-E14.5, mutant embryos are ~12% smaller than wild-type embryos

• by E15.0-E16.0, mutant embryos are ~25% smaller than wild-type embryos

cellular

abnormal cell physiology ( J:50865 )

• in culture, mutant MEFs show defective repair of ionizing radiation-induced DNA damage

• in culture, mutant MEFs show impaired V(D)J recombination, as shown by both recombination signal sequence (RSS) and coding-joining deficiencies

• impaired V(D)J recombination accounts for the blocked lymphopoiesis observed in older mutant embryos

increased cellular sensitivity to gamma-irradiation ( J:50865 )

• mutant MEFs show significantly increased sensitivity to ionizing radiation relative to wild-type MEFs

• in contrast, sensitivity to ultraviolet irradiation remains unaffected

decreased cell proliferation ( J:50865 )

• in culture, MEFs isolated from E13.5 homozygotes display significantly increased doubling times (55 hrs) relative to heterozygous (24 hrs) or wild-type MEFs (27 hrs)

• BrdU-labeling indicates a 23-34% reduction in the number of mutant MEFs found in the S phase of the cell cycle

• continuous BrdU-labeling of day 10 mutant MEFs and subsequent replating at low density shows impaired proliferative capacity and premature senescence

chromosome breakage ( J:80467 )

• cultured fibroblasts display chromosomal instability at a level of ~55%

immune system

small thymus ( J:50865 )

• at E15.0-E16.0, homozygotes exhibit a small thymus relative to wild-type embryos

decreased thymocyte number ( J:63078 )

• total thymocyte cellularity is reduced ~100-fold compared to wild-type

abnormal lymphopoiesis ( J:50865 )

abnormal B cell differentiation ( J:50865 )

• in culture, fetal liver cells from E15-E17.5 mutant embryos show a significant reduction in IgM⁺ B220⁺ B cells, indicating defective B-cell development

• nucleotide sequencing of potential rearrangements in DNA from mutant B-cell cultures revealed grossly abnormal DJ and V(D)J joins, with large deletions extending from one or both sides of the recombining segment

arrested B cell differentiation ( J:63078 )

• B cell development is arrested at the B220+ D43+ progenitor stage

abnormal T cell differentiation ( J:63078 )

• T lymphocyte development is arrested at the double negative (DN) stage

arrested T cell differentiation ( J:50865 )

• at E16.5-E17.5, mutant embryos exhibit an arrest of thymocyte development at the CD4^-CD8^-CD25⁺ stage, indicating a defect in productive rearrangement of T-cell antigen receptor beta genes

hematopoietic system

hematopoietic system phenotype ( J:50865 )

N	• at E15.0-E16.0, homozygotes appear grossly normal with no apparent anemia

small thymus ( J:50865 )

• at E15.0-E16.0, homozygotes exhibit a small thymus relative to wild-type embryos

decreased thymocyte number ( J:63078 )

• total thymocyte cellularity is reduced ~100-fold compared to wild-type

abnormal lymphopoiesis ( J:50865 )

abnormal B cell differentiation ( J:50865 )

• in culture, fetal liver cells from E15-E17.5 mutant embryos show a significant reduction in IgM⁺ B220⁺ B cells, indicating defective B-cell development

arrested B cell differentiation ( J:63078 )

• B cell development is arrested at the B220+ D43+ progenitor stage

abnormal T cell differentiation ( J:63078 )

• T lymphocyte development is arrested at the double negative (DN) stage

arrested T cell differentiation ( J:50865 )

• at E16.5-E17.5, mutant embryos exhibit an arrest of thymocyte development at the CD4^-CD8^-CD25⁺ stage, indicating a defect in productive rearrangement of T-cell antigen receptor beta genes

endocrine/exocrine glands

small thymus ( J:50865 )

• at E15.0-E16.0, homozygotes exhibit a small thymus relative to wild-type embryos

decreased thymocyte number ( J:63078 )

• total thymocyte cellularity is reduced ~100-fold compared to wild-type

Allelic Composition	Lig4^tm1Fwa/Lig4⁺
Genetic Background	involves: 129S6/SvEvTac * C57BL/6

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Lig4^tm1Fwa mutation (2 available); any Lig4 mutation (46 available)

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

cellular

chromosome breakage ( J:80467 )

• cultured fibroblasts display chromosomal instability at a level of ~32%

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 (2 available); any Lig4 mutation (46 available)
Tg(Cr2-cre)3Cgn mutation (2 available)
Xrcc4^tm2Fwa 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	Igh^tm2Cgn/Igh^tm2Cgn Igk^tm1Rsky/Igk^tm1Rsky Lig4^tm1Fwa/Lig4^tm1Fwa Trp53^tm1Tyj/Trp53^tm1Tyj
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)
Lig4^tm1Fwa mutation (2 available); any Lig4 mutation (46 available)
Trp53^tm1Tyj mutation (12 available); any Trp53 mutation (240 available)

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

hematopoietic system

abnormal class switch recombination ( J:126758 )

• class switching to IgG1 in B cells stimulated with anti-CD40 plus IL4 are 50% of wild-type

immune system

abnormal class switch recombination ( J:126758 )

• class switching to IgG1 in B cells stimulated with anti-CD40 plus IL4 are 50% of wild-type

Allelic Composition	Lig4^tm1Fwa/Lig4^tm1Fwa Trp53^tm1Brd/Trp53⁺
Genetic Background	involves: 129S6/SvEvTac * 129S7/SvEvBrd

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Lig4^tm1Fwa mutation (2 available); any Lig4 mutation (46 available)
Trp53^tm1Brd mutation (5 available); any Trp53 mutation (240 available)

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

mortality/aging

premature death ( J:63078 )

• majority of mice die at less than 8 weeks of age, with a significant drop in survival at ~3 weeks of age

prenatal lethality, incomplete penetrance ( J:63078 )

• embryonic lethality is dramatically abrogated in double mutants (20/369 double null offspring) compared to nearly total lethality with Lig4-deficiency alone (8/369 observed)

• numbers of double heterozygotes observed are similar to expected numbers

growth/size/body

decreased body weight ( J:63078 )

• postnatally, mice are much smaller (only 25% of control littermate weight) than wild-type or doubly-heterozygous littermates

nervous system

decreased neuron apoptosis ( J:63078 )

• neuronal apoptosis is significantly rescued with Trp53 haploinsufficiency

cellular

decreased neuron apoptosis ( J:63078 )

• neuronal apoptosis is significantly rescued with Trp53 haploinsufficiency

Allelic Composition	Lig4^tm1Fwa/Lig4^tm1Fwa Trp53^tm1Brd/Trp53^tm1Brd
Genetic Background	involves: 129S6/SvEvTac * 129S7/SvEvBrd

Find Mice

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

mortality/aging

premature death ( J:63078 )

• mice appear normal until 6 weeks of age, when survival drops precipitously

prenatal lethality, incomplete penetrance ( J:63078 )

• embryonic lethality is dramatically abrogated in double mutants (34/369 double null offspring) compared to nearly total lethality with Lig4-deficiency alone (8/369 observed)

• numbers of double heterozygotes observed are similar to expected numbers

growth/size/body

decreased body weight ( J:63078 )

• postnatally, mice are smaller (only 50% of control littermate weight) than wild-type or doubly-heterozygous littermates

cellular

increased cellular sensitivity to ionizing radiation ( J:63078 )

• cells are markedly sensitive to radiation

decreased neuron apoptosis ( J:63078 )

• low levels of pyknotic nuclei are observed between E12.5 and E14.5, indicating significant rescue of neuronal apoptosis which is seen in Lig4-deficient embryos

increased fibroblast proliferation ( J:63078 )

• cultured MEFs show significantly high rates of doubling compared to Lig4-deficient mice and are close to wild-type levels

immune system

decreased thymocyte number ( J:63078 )

• little rescue of thymocyte number is observed compared to Lig4-deficient mice

increased B cell number ( J:63078 )

• moderately increased B220+ CD43+ cell numbers are seen in bone marrow compared to Lig4-null, Trp53-heterozygous mice

hematopoietic system

decreased thymocyte number ( J:63078 )

• little rescue of thymocyte number is observed compared to Lig4-deficient mice

increased B cell number ( J:63078 )

• moderately increased B220+ CD43+ cell numbers are seen in bone marrow compared to Lig4-null, Trp53-heterozygous mice

nervous system

decreased neuron apoptosis ( J:63078 )

• low levels of pyknotic nuclei are observed between E12.5 and E14.5, indicating significant rescue of neuronal apoptosis which is seen in Lig4-deficient embryos

neoplasm

increased lymphoma incidence ( J:63078 )

• almost all (15/16) mice develop aggressive widely disseminated lymphoma which infiltrates the spleen, bone marrow, lymph nodes and thymus

endocrine/exocrine glands

decreased thymocyte number ( J:63078 )

• little rescue of thymocyte number is observed compared to Lig4-deficient mice

Allelic Composition	Xrcc5^tm1Dbr/Xrcc5^tm1Dbr Lig4^tm1Fwa/Lig4^tm1Fwa
Genetic Background	involves: 129S6/SvEvTac * C57BL/6

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Lig4^tm1Fwa mutation (2 available); any Lig4 mutation (46 available)
Xrcc5^tm1Dbr mutation (0 available); any Xrcc5 mutation (71 available)

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

mortality/aging

mortality/aging ( J:80467 )

N	• a small number of ^tm1Fwa, Xrcc5^tm1Dbr null animals (4/131) have reached maturity and are viable; this is equivalent to observed viability of Xrcc5-null animals

prenatal lethality, incomplete penetrance ( J:80467 )

• 4/131 Lig4/Xrcc5 double null animals have been live born compared to total lethality of Lig4 single null animals

immune system

abnormal lymphocyte morphology ( J:80467 )

• double mutants show lymphoid depletion similar to that observed in Xrcc5-deficient mice

hematopoietic system

abnormal lymphocyte morphology ( J:80467 )

• double mutants show lymphoid depletion similar to that observed in Xrcc5-deficient mice

digestive/alimentary system

abnormal small intestine morphology ( J:80467 )

• small intestines show smaller villi relative to wild-type and Xrcc5-deficient mice

cellular

chromosome breakage ( J:80467 )

• numbers of cultured cells show similar total percentage of chromosome aberrations to Xrcc4-deficient cells (~60% vs ~10% of wild-type cells)

Allelic Composition	Xrcc5^tm1Dbr/Xrcc5⁺ Lig4^tm1Fwa/Lig4⁺
Genetic Background	involves: 129S6/SvEvTac * C57BL/6

Find Mice

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

cellular

chromosome breakage ( J:80467 )

• cultured fibroblasts display chromosomal instability at a level of ~32%, similar to heterozygous Lig4 fibroblasts

Allelic Composition	Paxx^em1Spj/Paxx^em1Spj Lig4^tm1Fwa/Lig4^tm1Fwa
Genetic Background	involves: 129S6/SvEvTac * C57BL/6 * C57BL/6NTac

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Lig4^tm1Fwa mutation (2 available); any Lig4 mutation (46 available)
Paxx^em1Spj mutation (0 available); any Paxx mutation (11 available)

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

mortality/aging

prenatal lethality, complete penetrance ( J:236776 )

• no mice are born, similar to single Lig4^tm1Fwa homozygotes

Allelic Composition	Cdkn2a^tm1Rdp/Cdkn2a⁺ Lig4^tm1Fwa/Lig4^tm1Fwa
Genetic Background	involves: 129/Sv * 129S6/SvEvTac * C57BL/6J * SJL

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Cdkn2a^tm1Rdp mutation (6 available); any Cdkn2a mutation (67 available)
Lig4^tm1Fwa mutation (2 available); any Lig4 mutation (46 available)

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

mortality/aging

prenatal lethality, complete penetrance ( J:63078 )

• no doubly-deficient offspring are observed (0/170)

• numbers of double heterozygotes observed are similar to expected numbers

cellular

increased cellular sensitivity to ionizing radiation ( J:63078 )

• cells are highly sensitive to ionizing radiation compared to wild-type or Cdkn2a-deficient MEFs

increased neuron apoptosis ( J:63078 )

• high levels of pyknotic cells are observed in doubly-deficient embryos

decreased cell proliferation ( J:63078 )

• MEFs show premature growth arrest compared to wild-type MEFs

nervous system

increased neuron apoptosis ( J:63078 )

• high levels of pyknotic cells are observed in doubly-deficient embryos

Allelic Composition	Cdkn2a^tm1Rdp/Cdkn2a^tm1Rdp Lig4^tm1Fwa/Lig4^tm1Fwa
Genetic Background	involves: 129/Sv * 129S6/SvEvTac * C57BL/6J * SJL

Find Mice

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

mortality/aging

prenatal lethality, complete penetrance ( J:63078 )

• no doubly-deficient offspring are observed (0/170)

• numbers of double heterozygotes observed are similar to expected numbers

cellular

decreased cell proliferation ( J:63078 )

• MEFs show premature growth arrest compared to wild-type MEFs

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