Analysis Tools
mortality/aging
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• median survival is 333 days compared to 712 days for wild-type mice
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• Background Sensitivity: mice with an enriched C57BL/6 background exhibit 35% embryonic lethality unlike mice on a mixed 129S and C57BL/6 background
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• mice exhibit signs of premature aging including ulcerating wounds and premature death
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cellular
aneuploidy
(
J:151638
)
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• in primary epidermal cell cultures unlike in wild-type cells
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• at 1 month, mice stain positive for a senescence-associated marker in the bulge region, the dermal sheath, and papilla of hair follicles unlike in wild-type mice
• skin-derived precursors isolated from 1 month old mice exhibit increased staining for a marker of senescence and apoptosis compared with wild-type cells
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• primary epidermal cell cultures exhibit numerous cytogenetic aberrations unlike wild-type cells
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homeostasis/metabolism
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• at 1 month, mice fail to heal skin wounds after 6 days and exhibit reduced proliferation in the dermis of the wound compared to similarly treated wild-type mice
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digestive/alimentary system
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• mice develop epithelial esophagus cysts unlike wild-type mice
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gastric cyst
(
J:151638
)
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• mice develop epithelial stomach cysts unlike wild-type mice
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renal/urinary system
kidney cyst
(
J:151638
)
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• mice develop epithelial bladder cysts unlike wild-type mice
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skeleton
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• by 8 months, 25% of mice exhibit kyphosis
• by 10 months, 86% of mice exhibit kyphosis compared to 14% of wild-type mice
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integument
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• at 6 to 12 months, mice exhibit many areas without hair follicles unlike in wild-type mice
• at 6 to 12 months, 30% to 40% of mice exhibit hairless back skin unlike wild-type mice
• however, at 1 month mice exhibit normal hair follicle numbers
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blistering
(
J:151638
)
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• mice exhibit small skin blisters during early adulthood
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• by 1 months of age, 33% of mice develop ulcerating wounds on their dorsal and ventral sides that fail to heal unlike wild-type mice
• by 2 to 4 months, the remaining 67% of mice develop blisters and ulcerations unlike wild-type mice
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• epidermal cells from newborn mice fail to produce proliferating K5+ colonies when cultured unlike similarly treated wild-type cells
• however, newborn epdiermal cells will differentiate into K10+ cells following treatment with high calcium
• skin-derived precursors isolated young mice exhibit a 4- to 5-fold increase in proliferation compared with wild-type cells
• skin-derived precursors isolated from young mice exhibit 3- to 4-fold more robust self-renewal than wild-type cells
• however, differentiation and migratory capacity of skin-derived precursor cells are normal and skin-derived precursor hyperproliferation is rescued by transfection with p57Kip2 (Cdkn1c)
• skin-derived precursors isolated from 1 month old mice exhibit increased staining for a marker of senescence and apoptosis compared with wild-type cells
• dermal sheaths in 1 month old mice stains positive for gammaH2AX (H2afx), a marker of DNA damage unlike in wild-type mice
• 80% to 70% of skin-derived precursor cells isolated from 1 month old mice are positive for gammaH2AX (H2afx), a marker of DNA damage, unlike wild-type cells
• however, skin-derived precursor cells isolated from young mice do not stain positive for H2afx
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growth/size/body
gastric cyst
(
J:151638
)
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• mice develop epithelial stomach cysts unlike wild-type mice
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kidney cyst
(
J:151638
)
