Mouse Genome Informatics
hm1
    Trp63tm1.1Elrf/Trp63tm1.1Elrf
involves: 129S4/SvJae * 129S6/SvEvTac * C57BL/6
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
N
• Background Sensitivity: unlike mice on an enriched C57BL/6 background, mice do not exhibit embryonic lethality (J:151638)
• median survival is 333 days compared to 712 days for wild-type mice
• mice exhibit signs of premature aging including ulcerating wounds and premature death

cellular
• in primary epidermal cell cultures unlike in wild-type cells
• 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
• primary epidermal cell cultures exhibit numerous cytogenetic aberrations unlike wild-type cells

homeostasis/metabolism
• 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

digestive/alimentary system
• mice develop epithelial esophagus cysts unlike wild-type mice
• mice develop epithelial stomach cysts unlike wild-type mice

renal/urinary system
• mice develop epithelial bladder cysts unlike wild-type mice

skeleton
• by 8 months, 25% of mice exhibit kyphosis
• by 10 months, 86% of mice exhibit kyphosis compared to 14% of wild-type mice

integument
• 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
• mice exhibit small skin blisters during early adulthood
• 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
• epidermal cells from newborn mice fail to produce proliferating K5+ colonies when cultured unlike similarly treated wild-type cells
• 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
• 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, newborn epdiermal cells will differentiate into K10+ cells following treatment with high calcium
• however, differentiation and migratory capacity of skin-derived precursor cells are normal and skin-derived precursor hyperproliferation is rescued by transfection with p57Kip2 (Cdkn1c)
• however, skin-derived precursor cells isolated from young mice do not stain positive for H2afx


Mouse Genome Informatics
hm2
    Trp63tm1.1Elrf/Trp63tm1.1Elrf
involves: C57BL/6 * FVB/N
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• median survival is 333 days compared to 712 days for wild-type mice
• Background Sensitivity: mice with an enriched C57BL/6 background exhibit 35% embryonic lethality unlike mice on a mixed 129S and C57BL/6 background
• mice exhibit signs of premature aging including ulcerating wounds and premature death

cellular
• in primary epidermal cell cultures unlike in wild-type cells
• 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
• primary epidermal cell cultures exhibit numerous cytogenetic aberrations unlike wild-type cells

homeostasis/metabolism
• 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

digestive/alimentary system
• mice develop epithelial esophagus cysts unlike wild-type mice
• mice develop epithelial stomach cysts unlike wild-type mice

renal/urinary system
• mice develop epithelial bladder cysts unlike wild-type mice

skeleton
• by 8 months, 25% of mice exhibit kyphosis
• by 10 months, 86% of mice exhibit kyphosis compared to 14% of wild-type mice

integument
• 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
• mice exhibit small skin blisters during early adulthood
• 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
• 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


Mouse Genome Informatics
cx3
    Trp53tm1Tyj/Trp53tm1Tyj
Trp63tm1.1Elrf/Trp63tm1.1Elrf

either: (involves: 129S2/SvPas * C57BL/6 * FVB/N) or (involves: 129S2/SvPas * 129S4/SvJae * 129S6/SvEvTac * C57BL/6)
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
cellular
• skin-derived precursors isolated from 1 month old mice exhibit increased staining for a marker of senescence and decreased apoptosis compared with wild-type and Trp63tm1.1Elrf cells

integument
• after 8 days in culture, epidermal cells form fewer proliferating colonies than wild-type cells but more than Trp63 cells
• after 20 days in culture, epidermal cells fail to form proliferating colonies unlike similarly treated wild-type cells
• skin-derived precursors isolated from 1 month old mice exhibit increased staining for a marker of senescence and decreased apoptosis compared with wild-type and Trp63tm1.1Elrf cells