Phenotypes associated with this allele

• Allele Symbol: H2ax^tm1Fwa
• Allele Name: targeted mutation 1, Frederick W Alt
• Allele ID: MGI:2670743
• Summary: 5 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	H2ax^tm1Fwa/H2ax^tm1Fwa	involves: 129S6/SvEvTac	MGI:4438385
ht2	H2ax^tm1Fwa/H2ax^+	involves: 129S6/SvEvTac	MGI:4438386
cx3	Atm^tm1Fwa/Atm^tm1Fwa H2ax^tm1Fwa/H2ax^tm1Fwa	involves: 129S4/SvJae * 129S6/SvEvTac	MGI:3851149
cx4	H2ax^tm1Fwa/H2ax^tm1Fwa Trp53^tm1Brd/Trp53^tm1Brd	involves: 129S6/SvEvTac * 129S7/SvEvBrd * C57BL/6	MGI:2673482
cx5	H2ax^tm1Fwa/H2ax^+ Trp53^tm1Brd/Trp53^tm1Brd	involves: 129S6/SvEvTac * 129S7/SvEvBrd * C57BL/6	MGI:2673488

Genotype
MGI:4438385

hm1

• Allelic Composition: H2ax^tm1Fwa/H2ax^tm1Fwa
• Genetic Background: involves: 129S6/SvEvTac

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

cellular

chromosomal instability ( J:84879 )

• 52% of splenic T cells exhibit chromosomal abnormalities, including chromosomal gaps, fusions, fragments, and detached centromeres, compared to 11% in wild-type

growth/size/body

decreased body size ( J:84879 )

hematopoietic system

abnormal class switch recombination ( J:84879 )

• impaired class-switch recombination

decreased lymphocyte cell number ( J:84879 )

immune system

abnormal class switch recombination ( J:84879 )

• impaired class-switch recombination

decreased lymphocyte cell number ( J:84879 )

neoplasm

increased T cell derived lymphoma incidence ( J:84879 )

• 3 mutants succumb to aggressive CD4+/CD8+ thymic lymphomas, harboring translocations involving chromosomes 14 and 16, indicating a low level of increased tumor incidence

endocrine/exocrine glands

increased T cell derived lymphoma incidence ( J:84879 )

• 3 mutants succumb to aggressive CD4+/CD8+ thymic lymphomas, harboring translocations involving chromosomes 14 and 16, indicating a low level of increased tumor incidence

Genotype
MGI:4438386

ht2

• Allelic Composition: H2ax^tm1Fwa/H2ax⁺
• Genetic Background: involves: 129S6/SvEvTac

cellular

chromosomal instability ( J:84879 )

• 30% of splenic T cells exhibit chromosomal abnormalities, including chromosomal gaps, fusions, fragments, and detached centromeres compared to 11% in wild-type

Genotype
MGI:3851149

cx3

• Allelic Composition: Atm^tm1Fwa/Atm^tm1Fwa; H2ax^tm1Fwa/H2ax^tm1Fwa
• Genetic Background: involves: 129S4/SvJae * 129S6/SvEvTac

mortality/aging

embryonic lethality during organogenesis, complete penetrance ( J:138190 )

• because the two genes are 4 cm apart, the cross of heterozygote parents resulted in a 4% cross-over frequency of which half (2%) of the cross-overs had the two null alleles linked

• breeding of these progeny resulted in embryonic lethality in the double homozygotes

• half the embryos are dead at E11.5 and all embryos dead by E12.5

• embryos had pleiotropic developmental defects associated with increased cell death and decreased mitotic index

cellular

increased cell death ( J:138190 )

• freshly isolated E10.5 MEFs have a dramatic increase in the sub-G1 population, indicative of massive cell death

chromosomal instability ( J:138190 )

• 80% of E10.5 MEFs have cytogenetic abnormalities compared to 2-3% in wild-type controls

spontaneous chromosome breakage ( J:138190 )

• MEF metaphases contained numerous breaks per metaphase (average more than three abnormalities per abnormal metaphase), in contrast to one or, rarely, two aberrations per abnormal metaphase for controls

Genotype
MGI:2673482

cx4

• Allelic Composition: H2ax^tm1Fwa/H2ax^tm1Fwa; Trp53^tm1Brd/Trp53^tm1Brd
• Genetic Background: involves: 129S6/SvEvTac * 129S7/SvEvBrd * C57BL/6

mortality/aging

premature death ( J:84879 )

• die with lymphomas as early as 6 weeks of age, with 50% mortality by 10 weeks and most dead by 13 weeks

neoplasm

increased tumor incidence ( J:84879 )

• some mutants develop multiple cancers

increased colon adenocarcinoma incidence ( J:84879 )

• seen in some mutants with multiple cancers

increased T cell derived lymphoma incidence ( J:84879 )

• aggressive thymic lymphomas

increased B cell derived lymphoma incidence ( J:84879 )

• B220+/IgM- B lineage lymphomas and pro-B cell lymphomas; often harboring translocations involving chromosomes 12 (Igh) and 15 (Myc)

increased sarcoma incidence ( J:84879 )

• seen in some mutants with multiple cancers

digestive/alimentary system

increased colon adenocarcinoma incidence ( J:84879 )

• seen in some mutants with multiple cancers

endocrine/exocrine glands

increased T cell derived lymphoma incidence ( J:84879 )

• aggressive thymic lymphomas

Genotype
MGI:2673488

cx5

• Allelic Composition: H2ax^tm1Fwa/H2ax⁺; Trp53^tm1Brd/Trp53^tm1Brd
• Genetic Background: involves: 129S6/SvEvTac * 129S7/SvEvBrd * C57BL/6

mortality/aging

premature death ( J:84879 )

• 50% mortality by 17 weeks of age

neoplasm

increased lymphoma incidence ( J:84879 )

• develop lymphomas very early

increased T cell derived lymphoma incidence ( J:84879 )

increased B cell derived lymphoma incidence ( J:84879 )

• B lineage lymphomas, including Igmu+/IgL- pre-B cell lymphoma and IgM- B lineage lymphoma

• often harboring translocations involving chromosomes 12 (Igh) and 15 (Myc)

increased sarcoma incidence ( J:84879 )

increased teratoma incidence ( J:84879 )

• develop teratomas very early

endocrine/exocrine glands

increased T cell derived lymphoma incidence ( J:84879 )