Mouse Genome Informatics
cn1
    Lig4tm1Pmc/Lig4tm1Pmc
Trp53tm1Tyj/Trp53tm1Tyj
Tg(Nes-cre)1Kln/0

involves: 129S1/Sv * 129S2/SvPas * C57BL/6 * SJL
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• mice die by 32 weeks unlike Lig4tm1Pmc/Lig4tm1Pmc Tg(Nes-cre)1Kln mice with wild-type Trp53

tumorigenesis
• 94% of mice develop medulloblastoma beginning at 16 weeks


Mouse Genome Informatics
cn2
    Lig4tm1Pmc/Lig4tm1Pmc
Trp53tm1Tyj/Trp53tm1Tyj
Xrcc2tm2Pmc/Xrcc2tm2Pmc
Tg(Nes-cre)1Kln/0

involves: 129S1/Sv * 129S2/SvPas * C57BL/6 * SJL
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• mice die by 16 weeks

tumorigenesis
• 100% of mice develop medulloblastoma beginning at 14 weeks


Mouse Genome Informatics
cn3
    Lig4tm1Pmc/Lig4tm1Pmc
Trp53tm1Tyj/Trp53+
Xrcc2tm2Pmc/Xrcc2tm2Pmc
Tg(Nes-cre)1Kln/0

involves: 129S1/Sv * 129S2/SvPas * C57BL/6 * SJL
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• mice die by 32 weeks

tumorigenesis
• tumors exhibit a loss of heterozygosity at the Trp53 gene
• 75% of mice develop medulloblastoma beginning at 23 weeks


Mouse Genome Informatics
cn4
    Lig4tm1Pmc/Lig4tm1Pmc
Meox2tm1(cre)Sor/Meox2+

involves: 129S1/Sv * 129S4/SvJaeSor
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
nervous system
• mice exhibit neuraxis-wide apoptosis during development unlike in wild-type mice


Mouse Genome Informatics
cn5
    Lig4tm1Pmc/Lig4tm1Pmc
Tg(Nes-cre)1Kln/0

involves: 129S1/Sv * C57BL/6 * SJL
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
nervous system
N
• compared to germ line deletions of this gene, mice exhibit no increase in apoptosis during neural development (J:144617)


Mouse Genome Informatics
cn6
    Lig4tm1Pmc/Lig4tm1Pmc
Mre11atm1Jpt/Mre11atm1Jpt
Tg(Nes-cre)1Kln/0

involves: 129S1/SvImJ * 129S7/SvEvBrd * 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 microencephaly is rescued (J:144172)


Mouse Genome Informatics
cn7
    Lig4tm1Pmc/Lig4tm1Pmc
Nbntm1Jpt/Nbntm1Jpt
Tg(Nes-cre)1Kln/0

involves: 129S1/SvImJ * 129S7/SvEvBrd * C57BL/6 * SJL
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
nervous system
• at E13.5 and E15.5, neural tissue apoptosis is increased compared to in wild-type mice

growth/size


Mouse Genome Informatics
cn8
    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
nervous system
• at E13.5 and E15.5, neural tissue apoptosis is increased compared to in wild-type mice
• however, brain morphology is otherwise normal
• brain size is reduced as much as 40% compared to in littermate controls

homeostasis/metabolism
• DNA damage in the brain accumulates with age unlike in wild-type mice
• mice fail to repair ionizing radiation-induced DNA damage after 1 week compared to similarly treated wild-type mice that exhibit repair after 24 hours

behavior/neurological
• at 7 to 9 months, mice develop severe hind-limb ataxia or unknown etiology

cellular
• DNA damage in the brain accumulates with age unlike in wild-type mice
• mice fail to repair ionizing radiation-induced DNA damage after 1 week compared to similarly treated wild-type mice that exhibit repair after 24 hours

growth/size


Mouse Genome Informatics
cn9
    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)