All Phenotypes Mad2l1<tm1Sorg> MGI Mouse

Phenotypes associated with this allele

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Mad2l1^tm1Sorg/Mad2l1^tm1Sorg	involves: 129S2/SvPas * C57BL/6	MGI:3531554
ht2	Mad2l1^tm1Sorg/Mad2l1⁺	involves: 129S2/SvPas	MGI:3620040
ht3	Mad2l1^tm1Sorg/Mad2l1⁺	involves: 129S2/SvPas * C57BL/6	MGI:3531562
cx4	Mad2l1^tm1Sorg/Mad2l1⁺ Usp44^tm1.2Pjgl/Usp44^tm1.2Pjgl	involves: 129S2/SvPas * 129S4/SvJae * 129S7/SvEvBrd	MGI:5478537
cx5	Mad1l1^tm1.1Ktj/Mad1l1⁺ Mad2l1^tm1Sorg/Mad2l1⁺	involves: 129S2/SvPas * BALB/c * C57BL/6J	MGI:3698008

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

mortality/aging

embryonic lethality between implantation and somite formation, complete penetrance ( J:62829 )

• homozygous mutant embryos die in utero between E6.5 and E7.5

cellular

abnormal mitosis ( J:62829 )

• strikingly, ~25% of mitotic cells contain one or more lagging chromosomes, suggesting that anaphase proceeds in the absence of complete chromosome-microtubule attachment

• in utero, E6.5-E7.5 mutant embryos show a significant reduction in the total number of mitotic cells

abnormal mitotic spindle assembly checkpoint ( J:62829 )

• at E5.5, mutant embryonic cells assemble normal spindles and undergo mitosis but are unable to arrest in response to drug-induced spindle disruption, indicating loss of a functional spindle assembly checkpoint

• absence of a functional spindle assembly checkpoint allows mutant cells to proceed even when unattached chromosomes are present, resulting in widespread chromosome missegregation

abnormal inner cell mass apoptosis ( J:62829 )

• in vitro, cell death is restricted to the rapidly dividing cells of the inner cell mass

increased embryonic tissue cell apoptosis ( J:62829 )

• mutant embryos undergo programmed cell death after the initiation of gastrulation at E6.5-E7.5; at this stage, wild-type embryos contain only a few apoptotic cells near the embryo center

absent inner cell mass proliferation ( J:62829 )

• in vitro, the ICM of mutant embryos stops proliferating after E6.5

• in contrast, the postmitotic and highly polyploid trophoblast giant cells continue to grow in size through E8.5

embryo

embryo phenotype ( J:62829 )

N	• homozygous mutant embryos appear normal both in utero and in culture until E5.5

abnormal inner cell mass apoptosis ( J:62829 )

• in vitro, cell death is restricted to the rapidly dividing cells of the inner cell mass

increased embryonic tissue cell apoptosis ( J:62829 )

• mutant embryos undergo programmed cell death after the initiation of gastrulation at E6.5-E7.5; at this stage, wild-type embryos contain only a few apoptotic cells near the embryo center

absent inner cell mass proliferation ( J:62829 )

• in vitro, the ICM of mutant embryos stops proliferating after E6.5

• in contrast, the postmitotic and highly polyploid trophoblast giant cells continue to grow in size through E8.5

decreased embryo size ( J:62829 )

• mutant embryos are small relative to wild-type embryos

abnormal embryonic tissue morphology ( J:62829 )

• mutant embryos appear grossly abnormal relative to wild-type embryos

inner cell mass degeneration ( J:62829 )

• virtually no mutant ICM cells persist to E8.5

growth/size/body

decreased embryo size ( J:62829 )

• mutant embryos are small relative to wild-type embryos

Allelic Composition	Mad2l1^tm1Sorg/Mad2l1⁺
Genetic Background	involves: 129S2/SvPas

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Mad2l1^tm1Sorg mutation (1 available); any Mad2l1 mutation (14 available)

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

cellular

abnormal chromosome number ( J:117337 )

• chromosomal instability is much higher than in wild-type MEFs

aneuploidy ( J:105717 , J:117337 )

• at 5 months of age 15% of splenocytes are aneuploid; however no early aging related phenotypes are seen in heterozygotes at 19 to 27 months of age and no increase in the number of senescent MEFs is seen compared to wild-type (J:105717)

abnormal cell physiology ( J:117337 )

• 7.2% of MEFs are aneuploid for chromosome 2 compared to 1.4% of wild-type MEFs

• mutant MEFs injected into athymic nude mice produced tumors in 8/8 mice within 4 weeks compared to no tumors from wild-type MEFs; tumors are 40% smaller at 6 weeks compared to than produced by MEFs from Mad1/Mad2 mutants

neoplasm

increased incidence of induced tumors ( J:117337 )

• mutant MEFs induce tumors in 100% of athymic nude mice in 4 weeks

Allelic Composition	Mad2l1^tm1Sorg/Mad2l1⁺
Genetic Background	involves: 129S2/SvPas * C57BL/6

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Mad2l1^tm1Sorg mutation (1 available); any Mad2l1 mutation (14 available)

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

neoplasm

increased lung adenocarcinoma incidence ( J:67456 )

• at 18-19 months of age, heterozygotes show a high frequency of papillary lung adenocarcinomas relative to age-matched wild-type mice

• in contrast, the background rate of lymphomas detected in ageing heterozygotes remains unchanged relative to wild-type

cellular

cellular phenotype ( J:62829 )

N	• initial studies indicated that heterozygotes develop normally, with blastocysts exhibiting no evidence of a defective mitotic checkpoint as assayed by reactivity to phospho-histone 3 antibody; premature sister-chromatid separation was not examined in initial experiments

chromosome breakage ( J:67456 )

• MEFs from 4 out of 5 heterozygotes exhibit high frequencies of premature anaphase (sister-chromatid separation) relative to wild-type cultures

• all heterozygous MEF cultures display a significant increase in the number of aneuploid cells relative to wild-type cultures

• the % of aneuploid cells correlates with the severity of premature anaphase, suggesting a direct relationship between the severity of loss of checkpoint control and chromosome mis-segregation

hematopoietic system

increased spleen germinal center number ( J:62829 )

• heterozygotes are viable and largely normal but exhibit atypical (increased) germinal center formation in spleen relative to wild-type mice

immune system

increased spleen germinal center number ( J:62829 )

• heterozygotes are viable and largely normal but exhibit atypical (increased) germinal center formation in spleen relative to wild-type mice

respiratory system

increased lung adenocarcinoma incidence ( J:67456 )

• at 18-19 months of age, heterozygotes show a high frequency of papillary lung adenocarcinomas relative to age-matched wild-type mice

• in contrast, the background rate of lymphomas detected in ageing heterozygotes remains unchanged relative to wild-type

Allelic Composition	Mad2l1^tm1Sorg/Mad2l1⁺ Usp44^tm1.2Pjgl/Usp44^tm1.2Pjgl
Genetic Background	involves: 129S2/SvPas * 129S4/SvJae * 129S7/SvEvBrd

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Mad2l1^tm1Sorg mutation (1 available); any Mad2l1 mutation (14 available)
Usp44^tm1.2Pjgl mutation (0 available); any Usp44 mutation (42 available)

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

cellular

chromosomal instability ( J:193965 )

• chromosome instability is not exacerbated compared with cells form Mad2l1^tm1Sorg heterozygotes

Allelic Composition	Mad1l1^tm1.1Ktj/Mad1l1⁺ Mad2l1^tm1Sorg/Mad2l1⁺
Genetic Background	involves: 129S2/SvPas * BALB/c * C57BL/6J

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Mad1l1^tm1.1Ktj mutation (0 available); any Mad1l1 mutation (65 available)
Mad2l1^tm1Sorg mutation (1 available); any Mad2l1 mutation (14 available)

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

neoplasm

increased tumor incidence ( J:117337 )

• mutant MEFs induce tumors in 100% of athymic nude mice in 4 weeks

cellular

abnormal chromosome number ( J:117337 )

• chromosomal instability is much higher than in wild-type MEFs

aneuploidy ( J:117337 )

• 14.5% of MEFs are aneuploid for chromosome 2 compared to 1.4% of wild-type MEFs

abnormal cell physiology ( J:117337 )

• mutant MEFs injected into athymic nude mice produced tumors in 8/8 mice within 4 weeks compared to no tumors from wild-type MEFs

abnormal mitotic spindle assembly checkpoint ( J:117337 )

• stringency of spindle assembly checkpoint (SAC) mediated arrest in response to nocodazole is weaker in mutant MEFs

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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