Analysis Tools
cellular
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• mouse embryonic fibroblasts (MEFs) and white blood cells of G1 mice at 10 weeks of age from the first mouse generation (G1) exhibit telomere shortening
• successive generations of MEFs result in progressive telomere shortening as well as increased frequency of short telomeres and decreased frequency of long telomeres
• mice show progressively shorter telomeres in the lung, liver, and intestine of successive generations (G1-G4) at 10-12 weeks of age and in aged mice and in peripheral blood mononuclear cells at 70-100 weeks of age
• however, no changes in the amount of single-stranded G overhangs are seen
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• MEFs from G1 mice and intestine of G3 mice exhibit higher DNA damage amounts
• G1-G4 MEFs show an increase in the incidence of signal-free ends and end-to-end chromosome fusions and presence of diplochromosomes indicating telomere-mediated chromosomal aberrations
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digestive/alimentary system
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• G2 and G3 mice at 65-67 weeks of age exhibit increased frequency of intestinal degenerative pathologies characterized by epithelial and glandular atrophy with shortened villi and/or a decreased number of glands and cystic hyperplasia, and diffuse inflammatory reaction
• higher DNA damage burden is seen in the intestine of G3 mice
• G2-G3 mice show decreased levels of proliferation in the intestine
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• intestinal epithelial atrophy
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• intestinal glandular atrophy
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endocrine/exocrine glands
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• intestinal glandular atrophy
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• G2 and G3 mice at 65-67 weeks of age exhibit increased frequency of testis degenerative pathologies in which testes show low cellularity and maturation arrest in seminiferous tubules and in some instances focal testicular atrophy with the absence of germinal cells and an increase in Leydig or interstitial cells
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• increase in interstitial cells
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• focal testicular atrophy is seen in some instances
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growth/size/body
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• both males and females exhibit decreased body weight, though the difference does not reach significance in females
• decreased body weight is not aggravated with increasing mouse generations, with a 10% body weight reduction at 35 weeks of age in the 4 generations (G1-G2-G3-G4) mice
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homeostasis/metabolism
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• lungs exhibit BALT hyperplasia with hemosiderosis
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immune system
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• lungs exhibit bronchus-associated lymphoid tissue (BALT) hyperplasia with hemosiderosis, inflammatory infiltration, and focal thickening of the alveolar septa
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• 80% of G2 and 50% of G3 mice present with inflammatory lung phenotype
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reproductive system
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• G2 and G3 mice at 65-67 weeks of age exhibit increased frequency of testis degenerative pathologies in which testes show low cellularity and maturation arrest in seminiferous tubules and in some instances focal testicular atrophy with the absence of germinal cells and an increase in Leydig or interstitial cells
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• increase in interstitial cells
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• focal testicular atrophy is seen in some instances
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• no differences in litter size are seen between intercrosses of G1 and G2 homozygous mice, however a significant reduction in litter size is seen when G3 and G4 homozygotes are intercrossed to generated G4 and G5 mice
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respiratory system
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• 80% of G2 and 50% of G3 mice present with inflammatory lung phenotype
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• G2 and G3 mice at 65-67 weeks of age exhibit increased frequency of lung degenerative pathologies
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• focal thickening of the alveolar septa
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• G2-G3 mice show higher incidence of alpha-smooth muscle actin (SMA), indicating higher incidence of activated myofibroblasts and one G3 mouse presented with more then 50% of lung area covered by collagen fibers indicating lung profibrotic pathologies in old mice
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Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| idiopathic pulmonary fibrosis | DOID:0050156 | J:375765 | ||
