mortality/aging
• highly sensitive to radiation treatment
|
• about 75% of mice die by 4 weeks of age
• only 1 of 56 mice survived past 12 weeks of age
• bone marrow transplant from wild-type littermates at 2 weeks of age rescues much of the lethality
|
• about 75% of mice die by 4 weeks of age
|
hematopoietic system
• increase in nucleotide loss during coding joint formation similar to mice homozygous for Prkdcscid
|
• apparent arrest at the pro-B cell stage
|
• generalized decrease in the number of leukocytes
• average number of nucleated cells is reduced at 2 weeks of age
|
• in the peripheral blood
|
• in the peripheral blood
|
• in the peripheral blood
|
• in the bone marrow
|
• drastically reduced lymphocyte numbers at 2 weeks of age
|
• few mature B cells are found in the spleen
|
• unlike in null mice, double positive and single positive T cells are present although in reduced numbers
• decrease in the number of cells expressing TCRB
|
• severe reduction of double-negative thymocytes at different developmental stages
|
• in the bone marrow
|
• decrease in the number of (Lin-Sca-1+c-Kit+ (LSK) cells in the liver at E14.5
• severe reduction (100 fold) in the number of bone marrow LSK cells at P1
• near ablation of bone marrow LSK cells at 2 weeks of age
|
pancytopenia
(
J:171351
)
• in the peripheral blood beginning at 2 weeks of age
• bone marrow transplant from wild-type littermates at 2 weeks rescues pancytopenia
|
• cells isolated at E12.5 proliferate normally for 24h then slow down and collapse due to massive cell death by 72h in culture
• fetal liver LSK cells are unable to repopulate in vivo
• fetal liver LSK cells show an increase in spontaneous DNA lesions and apoptosis
|
cellular
• MEFs display increased sensitivity to replication stress inducers, including UV irradiation, camptothecin, and mitomycin C
|
• most striking response is to mitomycin C
|
• highly sensitive to radiation treatment
• MEFs are hypersensitive to ionizing radiation induced cell death
|
• expression analysis in MEFs following DNA damage indicates abnormalities in the homologous recombination/Fanconi anemia pathway
|
growth/size/body
• become apparently smaller within 2?3 weeks of birth
• bone marrow transplant from wild-type littermates at 2 weeks of age improves growth
|
immune system
• increase in nucleotide loss during coding joint formation similar to mice homozygous for Prkdcscid
|
• apparent arrest at the pro-B cell stage
|
• in the peripheral blood
|
• in the bone marrow
|
• drastically reduced lymphocyte numbers at 2 weeks of age
|
• few mature B cells are found in the spleen
|
• unlike in null mice, double positive and single positive T cells are present although in reduced numbers
• decrease in the number of cells expressing TCRB
|
• severe reduction of double-negative thymocytes at different developmental stages
|
• in the bone marrow
|
• drastically attenuated at 2 weeks of age
|
integument
digestive/alimentary system
homeostasis/metabolism
• expression analysis in MEFs following DNA damage indicates abnormalities in the homologous recombination/Fanconi anemia pathway
|
• highly sensitive to radiation treatment
|
pigmentation
• hyperpigmentation of the footpad and tail apparent by 1 week of age
|