Phenotypes associated with this allele
Allelic
Composition |
Ercc6ltm1.2Ajlc/Ercc6l+
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Genetic
Background |
involves: 129S2/SvPas * C57BL/6J * C57BL/6N * SJL/J |
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| Find Mice |
Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Ercc6ltm1.2Ajlc mutation
(0 available);
any
Ercc6l mutation
(6 available)
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mortality/aging
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• heterozygous females are obtained at sub-Mendelian ratios at 4 weeks of age, with ~20% dying either during the later stages of embryonic development or perinatally
• however, Mendelian ratios, embryo size and morphology are normal at E10.5, E11.5 and 12.5, and surviving females show normal appearance and body weight at ~1 year of age
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reproductive system
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• two of the heterozygous females studied did not produce any viable pups
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• most heterozygous females exhibit reduced fertility
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• heterozygous females mated with wild-type males produce fewer pups than wild-type females (4.6 +/- 2.3 versus 15.8 +/- 2.9) over a 14-week period
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cellular
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• MEFs obtained from E11.5 embryos show a mild but significant increase in the number of 53BP1 foci and micronuclei relative to wild-type MEFs
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• MEFs are refractory to RASV12/E1A-induced transformation, giving rise to a smaller number of colonies than wild-type MEFs
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• in culture, MEFs obtained from E11.5 embryos proliferate at a slightly lower rate than wild-type MEFs
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• MEFs obtained from E11.5 embryos show a mild but significant increase in the number of 53BP1 foci and micronuclei relative to wild-type MEFs
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| Find Mice |
Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Ercc6ltm1.2Ajlc mutation
(0 available);
any
Ercc6l mutation
(6 available)
Trp53tm1Tyj mutation
(12 available);
any
Trp53 mutation
(232 available)
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mortality/aging
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• no viable mice are born
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embryo
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• at E10.5, embryos show a significant increase in the number of apoptotic cells, as determined by IHC staining for cleaved caspase-3
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cellular
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• at E10.5, embryos show a significant increase in the number of apoptotic cells, as determined by IHC staining for cleaved caspase-3
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• at E10.5, embryos exhibit an increase in the proportion of gamma-H2AX-positive cells relative to wild-type embryos
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| Find Mice |
Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Ercc6ltm1.2Ajlc mutation
(0 available);
any
Ercc6l mutation
(6 available)
Trp53tm1Tyj mutation
(12 available);
any
Trp53 mutation
(232 available)
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mortality/aging
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• no viable mice are born, suggesting that p53-dependent apoptosis and senescence are unlikely to be the only drivers of embryonic lethality
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embryo
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• at E10.5, embryos show a significant increase in the number of apoptotic cells, as determined by IHC staining for cleaved caspase-3
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• embryos are smaller at E10.5
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growth/size/body
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• embryos are smaller at E10.5
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cellular
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• at E10.5, embryos show a significant increase in the number of apoptotic cells, as determined by IHC staining for cleaved caspase-3
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• at E10.5, embryos exhibit an increase in the proportion of gamma-H2AX-positive cells relative to wild-type embryos
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| Find Mice |
Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Ercc6ltm1.2Ajlc mutation
(0 available);
any
Ercc6l mutation
(6 available)
Trp53tm1Tyj mutation
(12 available);
any
Trp53 mutation
(232 available)
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mortality/aging
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• only one female is born out of 7 expected, indicating that the proportion of viable births is further reduced in a Trp53 null background
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Allelic
Composition |
Ercc6ltm1.2Ajlc/Y
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Genetic
Background |
involves: 129S2/SvPas * C57BL/6J * C57BL/6N * SJL/J |
|
| Find Mice |
Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Ercc6ltm1.2Ajlc mutation
(0 available);
any
Ercc6l mutation
(6 available)
|
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mortality/aging
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• male embryos are obtained at a lower than expected frequency at E10.5, E11.5, E12.5, and E13.5
• most embryos lose viability at or before E13.5 and no males are born
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embryo
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• at E10.5, embryos show a significant increase in the number of apoptotic cells, as determined by IHC staining for cleaved caspase-3
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• male embryos show a general developmental arrest at E12.5 and E13.5
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• male embryos are grossly normal but smaller at E10.5; embryo length reduction becomes more evident after E11.5
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growth/size/body
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• male embryos are grossly normal but smaller at E10.5; embryo length reduction becomes more evident after E11.5
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nervous system
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• at E10.5, embryos show a significant increase in the number of cleaved caspase-3-positive cells in the brain
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cellular
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• mouse embryonic fibroblasts (MEFs) obtained from E11.5 and E12.5 embryos exhibit increased levels of 53BP1 nuclear foci and micronucleus formation
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• MEFs obtained from E11.5 and E12.5 embryos exhibit polyploidy
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• MEFs are resistant to RASV12/E1A-induced transformation, as indicated by their inability to form colony colonies
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• MEFs obtained from E11.5 and E12.5 embryos show a greater tendency to accumulate in the G2 cell-cycle phase relative to wild-type MEFs
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• at E10.5, embryos show a significant increase in the number of apoptotic cells, as determined by IHC staining for cleaved caspase-3
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• at E10.5, embryos show a significant increase in the number of cleaved caspase-3-positive cells in the brain
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• in culture, MEFs obtained from E11.5 and E12.5 embryos proliferate at a lower rate than wild-type MEFs from passage one and stop proliferating after 4 passages
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• MEFs obtained from E11.5 and E12.5 embryos enter into a senescent state after only 3-4 passages in culture, as determined by senescence-associated beta-galactosidase staining
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• at early passages, MEFs obtained from E11.5 and E12.5 embryos exhibit poor EdU incorporation, indicating a very limited replicative capacity
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• at E10.5, embryos exhibit an increase in the proportion of gamma-H2AX-positive cells; DNA damage is detected in all embryonic tissues but is particularly evident in embryonic brain
• a high number of p53 positive cells is observed throughout the embryo at E10.5 and onward, indicating extensive p53 activation
• MEFs obtained from E11.5 and E12.5 embryos show phenotypes associated with genome instability, including increased levels of 53BP1 nuclear foci, micronucleus formation and polyploidy
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homeostasis/metabolism
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