Mouse Genome Informatics
hm1
    H2afxtm1Fwa/H2afxtm1Fwa
involves: 129S6/SvEvTac
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
cellular
• 52% of splenic T cells exhibit chromosomal abnormalities, including chromosomal gaps, fusions, fragments, and detached centromeres, compared to 11% in wild-type

growth/size

hematopoietic system
• impaired class-switch recombination

immune system
• impaired class-switch recombination

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


Mouse Genome Informatics
ht2
    H2afxtm1Fwa/H2afx+
involves: 129S6/SvEvTac
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
cellular
• 30% of splenic T cells exhibit chromosomal abnormalities, including chromosomal gaps, fusions, fragments, and detached centromeres compared to 11% in wild-type


Mouse Genome Informatics
cx3
    Atmtm1Fwa/Atmtm1Fwa
H2afxtm1Fwa/H2afxtm1Fwa

involves: 129S4/SvJae * 129S6/SvEvTac
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• 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
• freshly isolated E10.5 MEFs have a dramatic increase in the sub-G1 population, indicative of massive cell death
• 80% of E10.5 MEFs have cytogenetic abnormalities compared to 2-3% in wild-type controls
• 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


Mouse Genome Informatics
cx4
    H2afxtm1Fwa/H2afxtm1Fwa
Trp53tm1Brd/Trp53tm1Brd

involves: 129S6/SvEvTac * 129S7/SvEvBrd * C57BL/6
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• die with lymphomas as early as 6 weeks of age, with 50% mortality by 10 weeks and most dead by 13 weeks

tumorigenesis
• some mutants develop multiple cancers
• B220+/IgM- B lineage lymphomas and pro-B cell lymphomas; often harboring translocations involving chromosomes 12 (Igh) and 15 (Myc)
• aggressive thymic lymphomas
• seen in some mutants with multiple cancers
• seen in some mutants with multiple cancers


Mouse Genome Informatics
cx5
    H2afxtm1Fwa/H2afx+
Trp53tm1Brd/Trp53tm1Brd

involves: 129S6/SvEvTac * 129S7/SvEvBrd * C57BL/6
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• 50% mortality by 17 weeks of age

tumorigenesis
• develop lymphomas very early
• 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)
• develop teratomas very early