Mouse Genome Informatics
hm1
    Atmtm1Pmc/Atmtm1Pmc
involves: 129X1/SvJ * C57BL/6
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
cellular
• ionizing radiation fails to induce cell death; irradiation-induced cell death is almost absent in the hippocampal dentate gyrus, cerebellum, and cerebral cortex compared to wild-type
• only occasional dead cells are found in the external granule layer of the cerebellum whereas widespread cell death is observed in wild-type after irradiation
• in the retina no apoptosis is seen in the center of the retina compared to wild-type, but apoptosis occurs in the periphery of the irradiated retina of mutant and wild-type mice
• cell death in the subventricular zone after irradiation is present but reduced compared to wild-type

reproductive system
• mice are sterile

tumorigenesis
• mice are prone to lymphoma

Mouse Models of Human Disease
OMIM IDRef(s)
Ataxia-Telangiectasia; AT 208900 J:47752


Mouse Genome Informatics
hm2
    Atmtm1Pmc/Atmtm1Pmc
Not Specified
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
cellular
• mutant mouse embryonic fibroblasts (MEFs) show radiation-resistant DNA synthesis following ionizing radiation, indicating impaired intra-S-phase checkpoint
• G1/S-phase checkpoint is defective in gamma-irradiated thymic cells
• thymocytes are more resistant than wild-type thymocytes to gamma radiation-induced apoptosis but more sensitive than either Chek2tm1Mak or Trp53tm1Brd thymocytes


Mouse Genome Informatics
cn3
    Atmtm1Pmc/Atmtm1Pmc
Lig4tm1Pmc/Lig4tm1Pmc
Tg(Nes-cre)1Kln/0

involves: 129S1/SvImJ * C57BL/6 * SJL
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
behavior/neurological
• at 7 to 9 months, mice develop severe hind-limb ataxia or unknown etiology

nervous system
N
• unlike in mice with Lig4tm1Pmc/Lig4tm1Pmc Tg(Nes-cre)1Kln, mice do not exhibit any increased apoptosis in the nervous system, and microcephaly is rescued (J:144172)


Mouse Genome Informatics
cx4
    Atmtm1Pmc/Atmtm1Pmc
Lig4tm1Icrf/Lig4tm1Icrf

either: (involves: 129P2/OlaHsd) or (involves: 129S1/Sv * 129X1/SvJ)
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• mice are born alive but die within 2 hours (J:65540)
• mice do not survive past P1 (J:111068)

growth/size/body
• newborns are significantly smaller than wild-type littermates

nervous system
• double mutants show a complete attenuation of apoptosis in the nervous system at all stages between E11.5 and E15.5 (J:65540)
• almost no apoptosis is observed compared to Lig4-deficient brains (J:111068)

cellular
• double mutants show a complete attenuation of apoptosis in the nervous system at all stages between E11.5 and E15.5 (J:65540)
• almost no apoptosis is observed compared to Lig4-deficient brains (J:111068)


Mouse Genome Informatics
cx5
    Atmtm1Pmc/Atmtm1Pmc
Lig4tm1Icrf/Lig4+

either: (involves: 129P2/OlaHsd) or (involves: 129S1/Sv * 129X1/SvJ)
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
nervous system
• extensive apoptosis occurs in the spinal cord at E11.5 and the developing cortex at E14.5

cellular
• extensive apoptosis occurs in the spinal cord at E11.5 and the developing cortex at E14.5


Mouse Genome Informatics
cx6
    Atmtm1Pmc/Atm+
Lig4tm1Icrf/Lig4tm1Icrf

either: (involves: 129P2/OlaHsd) or (involves: 129S1/Sv * 129X1/SvJ)
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
nervous system
• extensive apoptosis occurs in the spinal cord at E11.5 and the developing cortex at E14.5

cellular
• extensive apoptosis occurs in the spinal cord at E11.5 and the developing cortex at E14.5


Mouse Genome Informatics
cx7
    Atmtm1Pmc/Atmtm1Pmc
Lig4tm1Icrf/Lig4tm1Icrf

involves: 129
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging

cellular
• ionizing radiation-induced apoptosis in the developing nervous system is almost completely blocked


Mouse Genome Informatics
cx8
    Atmtm1Pmc/Atmtm1Pmc
Trp73tm2Mak/Trp73tm2Mak

involves: 129P2/OlaHsd * C57BL/6J
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
hematopoietic system
• the increased apoptosis in response to DNA damaging agents is reversed compared to Trp73 tm2Mak single mutants, with cells showing reisistance to apoptosis similar to that in Atmtm1Pmc single mutants

immune system
• the increased apoptosis in response to DNA damaging agents is reversed compared to Trp73 tm2Mak single mutants, with cells showing reisistance to apoptosis similar to that in Atmtm1Pmc single mutants

cellular
• the increased apoptosis in response to DNA damaging agents is reversed compared to Trp73 tm2Mak single mutants, with cells showing reisistance to apoptosis similar to that in Atmtm1Pmc single mutants
• the increased thymocyte apoptosis in response to gamma-irradiation is reversed compared to mice homozygous for Trp73 tm2Mak single mutants, with cells showing reisistance to apoptosis similar to that in Atmtm1Pmc single mutants

endocrine/exocrine glands
• the increased apoptosis in response to DNA damaging agents is reversed compared to Trp73 tm2Mak single mutants, with cells showing reisistance to apoptosis similar to that in Atmtm1Pmc single mutants


Mouse Genome Informatics
cx9
    Xrcc2tm1Pmc/Xrcc2tm1Pmc
Atmtm1Pmc/Atmtm1Pmc

involves: 129S1/Sv
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• embryos are recovered at the same frequency as Xrcc2 single mutants indicating Atm deficiency does not provide a survival advantage