Phenotypes Associated with This Genotype

Genotype
MGI:3719052

cx48

• Allelic Composition: Cdkn2a^tm1Rdp/Cdkn2a^tm1Rdp; Terc^tm1Rdp/Terc^tm1Rdp
• Genetic Background: involves: 129/Sv * C57BL/6J * SJL

• ♀: phenotype observed in females
• ♂: phenotype observed in males
• N: normal phenotype

Degenerative phenotypes, including increased apoptosis in gastrointestinal crypts and germ cell depletion, in Terc^tm1Rdp/Terc^tm1Rdp and Cdkn2a^tm1Rdp/Cdkn2a^tm1Rdp Terc^tm1Rdp/Terc^tm1Rdp mice

mortality/aging

premature aging ( J:120065 )

• 12- to 13-week old late generation (G4) mutants exhibit accelerated degeneration as indicated by hair graying, alopecia, kyphosis, reduced body size and weight, and fragility

neoplasm

increased tumor incidence ( J:120065 )

• 98% of early generation mutants succumb to tumors with a median tumor-free latency of 38.6 weeks

• late generation mutants show a decrease in percent tumor death and an increase in tumor-free latency, from 98% to 43% and 38.6-65.3 weeks compared to early generation mutants

increased lymphoma incidence ( J:120065 )

• 11% and 10% of early generation and late generation mutants, respectively, develop lymphomas

increased sarcoma incidence ( J:120065 )

• 57% and 59% of early generation and late generation mutants, respectively, develop histocytic sarcomas

• 24% and 28% of early generation and late generation mutants, respectively, develop soft tissue sarcomas

cellular

abnormal telomere length ( J:120065 )

• the anaphase bridge index (ABI) is increased to the same extent as in Terc^tm1Rdp homozygotes in late-generation (G4/G5) intestinal crypts indicating telomere dysfunction

increased male germ cell apoptosis ( J:120065 )

♂ • apoptotic depletion of germ cells in late generation mutants

decreased cell proliferation ( J:120065 )

• MEFs grown in culture show decreased growth rates after 10 population doublings with steady slow proliferation thereafter, indicating that telomere dysfunction suppresses the growth rate

• early generation (G0) astrocytes show continuous proliferation whereas the late generation (G4) astrocytes senesce after 2.5 population doublings, indicating that telomere dysfunction constrains the immortalization potential of astrocytes

reproductive system

increased male germ cell apoptosis ( J:120065 )

♂ • apoptotic depletion of germ cells in late generation mutants

testicular atrophy ( J:120065 )

♂ • testicular atrophy and associated apoptotic depletion of germ cells in late generation mutants

growth/size/body

decreased body size ( J:120065 )

• late generation mutants have reduced body size and are fragile

decreased body weight ( J:120065 )

• late generation mutants have reduced body weight

digestive/alimentary system

abnormal intestine morphology ( J:120065 )

• the GI crypts of late generation mutants exhibit high levels of apoptosis

skeleton

kyphosis ( J:120065 )

• late generation mutants exhibit kyphosis

endocrine/exocrine glands

testicular atrophy ( J:120065 )

♂ • testicular atrophy and associated apoptotic depletion of germ cells in late generation mutants