Table 2.
Comparison of diverse mouse strains with accelerated aging due to genomic instability.
Ercc1-/- | Ercc1-/Δ | Bubr1H/H | polγD257A/D257A | |
---|---|---|---|---|
Human disease modeled | XFE progeria syndrome | XFE progeria syndrome | Mosaic Variegated Aneuploidy | None |
Mutated gene | Ercc1 | Ercc1 | Bubr1 | Polg |
Consequence of mutation | Compromised in multiple DNA repair pathways | Compromised in multiple DNA repair pathways | Defective mitotic spindle assembly checkpoint | Inability to proofread newly synthesized mtDNA |
% Normal protein expression | 0% | 10% | 10% | 0% |
Pathologies | ||||
Growth retardation* | + | + | + | - |
Kyphosis | + | + | + | + |
Sarcopenia | + | + | + | + |
Skin changes& | + | - | + | + |
Hematologic abnormalities# | + | - | - | + |
SQ fat loss | - | - | + | + |
Neurologic abnormalities˄ | + | + | + | - |
Osteoporosis | - | + | - | + |
Hearing loss | - | + | - | + |
Hematopoietic organ atrophy and/or involution% | - | + | - | + |
Impaired vision$ | - | + | + | - |
Cardiovascular abnormalities | - | + | + | + |
Other | Liver failure | Disc degeneration, renal dysfunction; infertility | Impaired wound healing, facial dysmorphisms, cachexia, infertility | Loss of intestinal crypts and intestinal dysplasia, infertility |
Lifespan | 3-4 weeks (McWhir and others 1993; Niedernhofer and others 2006; Weeda and others 1997) | Median: 16 weeks; maximum: 29 weeks (Dolle and others 2011) | Median: 6 months (Baker and others 2004) | Median: 48 weeks; maximum: 61 weeks (Trifunovic and others 2004) Median: 416 days; maximum: 460 days (Kujoth and others 2005) |
Premature cell senescence? | + | + | + | - |
Growth retardation includes runting and dwarfism
Skin changes include atrophy, reduced dermal thickness, hair graying, and alopecia
Hematologic abnormalities include leukopenia and thrombocytopenia
Neurologic abnormalities include dystonia, tremors, ataxia, neurodegeneration, brain and/or spinal cord astrocytosis and microgliosis
Hematopoietic organs include spleen and thymus
Impaired vision includes cataracts