Phenotypes Associated with This Genotype

Genotype
MGI:4820641

cx8

• Allelic Composition: Pms2^tm1Lisk/Pms2^tm1Lisk; Terc^tm1Rdp/Terc^tm1Rdp
• Genetic Background: involves: 129/Sv * 129S2/SvPas * C57BL/6 * C57BL/6J * SJL

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

mortality/aging

mortality/aging ( J:125218 )

N • mice exhibit increased survival compared with single homozygotes

neoplasm

increased lymphoma incidence ( J:125218 )

• mice exhibit increased incidence of lymphomas compared with Terc^tm1Rdp homozygotes

• incidence of lymphomas decreases in successive generations

increased carcinoma incidence ( J:125218 )

• mice exhibit increased incidence of carcinomas compared with Terc^tm1Rdp homozygotes

• however, the incidence of carcinomas after three generations is normal

increased sarcoma incidence ( J:125218 )

• mice exhibit increased incidence of histiocytic sarcomas compared with Terc^tm1Rdp homozygotes

• however, the incidence of histiocytic sarcomas after three generations is normal

cellular

decreased telomere length ( J:125218 )

• telomeres in mouse embryonic fibroblasts or from small intestine sections become progressively shorter each generation compared to in cells from Terc^tm1Rdp homozygotes

abnormal cell physiology ( J:125218 )

• independent of telomere length, mouse embryonic fibroblasts (MEFs) undergo immortalization after fewer passages compared with cells from Terc^tm1Rdp homozygotes

• sister chromatid exchange in mouse embryonic fibroblasts is increased compared to in wild-type cells

increased enterocyte apoptosis ( J:125218 )

• compared with wild-type mice and third generation Terc^tm1Rdp homozygotes

abnormal DNA repair ( J:125218 )

• cells from the small intestine exhibit an increase in gamma-H2AX foci, indicative of DNA damage, compared with cells from wild-type mice

chromosomal instability ( J:125218 )

• mouse embryonic fibroblasts (MEFs) exhibit fewer chromosomal breaks and fragmentations compared with MEFs from Pms2^tm1Lisk

• MEFs exhibit in increase in microsatellite instability compared with wild-type cells

• end-to-end chromosome fusions in MEFs are increased compared to in cells from wild-type mice and Terc^tm1Rdp homozygotes

• however, mice exhibit rescue of increased bivalent recombination figures and chromatid cross-links observed in cells from Terc^tm1Rdp homozygotes and partial rescue of the complex chromosome aberrations, chromosomes fusions, and minichromosomes observed in cells from Pms2^tm1Lisk homozygotes

digestive/alimentary system

digestive/alimentary phenotype ( J:125218 )

N • unlike in Terc^tm1Rdp homozygotes, proliferation of intestinal cells is rescued after 2 generations

increased enterocyte apoptosis ( J:125218 )

• compared with wild-type mice and third generation Terc^tm1Rdp homozygotes

abnormal intestine morphology ( J:125218 )

• mice exhibit reduced intestinal atrophy compared with Terc^tm1Rdp homozygotes

homeostasis/metabolism

abnormal DNA repair ( J:125218 )

• cells from the small intestine exhibit an increase in gamma-H2AX foci, indicative of DNA damage, compared with cells from wild-type mice