Analysis Tools
mortality/aging
| N |
• unexpectedly, mice are born at expected Mendelian ratios, viable, and do not exhibit any gross abnormalities
|
growth/size/body
 |
• male mice are slightly smaller than wild-type controls until 15 weeks of age, suggesting a mild growth defect
|
|
|
• males show a slight but statistically significant decrease in body weight until 15 weeks of age but no differences in body weight, tissue weight, or body length at 21-22 of age, indicating that males eventually attain normal body weight in adulthood
• females show a non-significant decrease in body weight in early life but have normal body weight, body length, and tissue weight in adulthood
|
cellular
|
• primary mouse embryonic fibroblasts (MEFs) subjected to irradiation and incubated for 14 days show reduced ability to form colonies using clonogenic assays, indicating increased radiosensitivity
|
|
• after treatment with doxorubicin (a DNA damaging agent), primary MEFs isolated from E13.5 embryos rapidly cease proliferating and exhibit significantly higher mRNA expression of multiple senescence markers (Cdkn2a/p16INK4a, Il6, Mmp3 and Ccl2) than similarly treated wild-type MEFs
• under the standard 3T3 protocol, MEFs show a rapid reduction in proliferation and prematurely enter replicative crisis after serial passage
|
|
• primary MEFs show significantly higher TRP53 (p53) protein levels than wild-type MEFs at passage 4, suggesting higher basal activation of p53
• MEFs treated with low doses of doxorubicin for 24 h show a significant rise in mRNA expression of classical p53 target genes (Cdkn1a, Pml and Serpine1), indicating higher p53 activity
• under the standard 3T3 protocol, MEFs show a significant increase in total and phosphorylated p53 levels at passage 7, consistent with elevated p53 activation
• however, no significant shift is noted under basal conditions in the expression of genes involved in cell cycle arrest, cellular senescence, and cell death in the thymus, heart or liver of male and female mice
|
|
• primary MEFs exhibit impaired proliferation in response to DNA damage and replicative stress
|
homeostasis/metabolism
|
• after 2 rounds of 4 Gy total body irradiation, mice show a greater weight loss than irradiated wild-type controls, with females exhibiting a more pronounced effect than males; both sexes show a significantly smaller heart than wild-type controls
• 8 h after a single dose of irradiation (4 Gy), males show significantly higher mRNA levels of p53 target genes (e.g. Cdkn1a, Gadd45a, Serpine1, Bax, and Fas) in the heart; Cdkn1a and Serpine1 expression is also upregulated in the male thymus, while a number of genes involved in transmembrane receptor signaling, cell adhesion, and growth are downregulated in the male heart
• 2 h after 4 Gy total body irradiation, females show a significant rise in Cdkn1a mRNA expression in the heart, with no upregulation of other p53 target genes noted in the heart or thymus
• however, both sexes show the expected rapid increase in gamma-H2AX levels in the heart and thymus at 2 h after 4 Gy total body irradiation
|
cardiovascular system
|
• 8 weeks after the first round of total body irradiation, both male and female mice show a significantly lower heart weight than similarly irradiated wild-type controls
• however, no significant changes are noted in testis-, kidney-, spleen-, liver-, or thymus weight after irradiation
|
neoplasm
| N |
• after a single intramuscular injection of 3-methylcholanthrene (3MC) into the hindlimb, mice of both sexes develop high-grade sarcomas with significantly higher mRNA and protein levels of CDKN1A (p21), but no differences in tumor initiation, overall survival, tumor mass or tumor diameter at sacrifice relative to 3MC-treated wild-type controls
|
