Phenotypes associated with this allele

• Allele Symbol: Pms2^tm1Lisk
• Allele Name: targeted mutation 1, Michael Liskay
• Allele ID: MGI:1857947
• Summary: 5 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Pms2^tm1Lisk/Pms2^tm1Lisk	involves: 129S2/SvPas	MGI:4819010
hm2	Pms2^tm1Lisk/Pms2^tm1Lisk	involves: 129S2/SvPas * C57BL/6	MGI:2663888
ht3	Pms2^tm1Lisk/Pms2^+	involves: 129S2/SvPas	MGI:4820592
cx4	Pms2^tm1Lisk/Pms2^tm1Lisk Terc^tm1Rdp/Terc^tm1Rdp	involves: 129/Sv * 129S2/SvPas * C57BL/6 * C57BL/6J * SJL	MGI:4820641
cx5	Apc^Min/Apc^+ Pms2^tm1Lisk/Pms2^tm1Lisk	involves: 129S2/SvPas * C57BL/6J	MGI:4820588

Genotype
MGI:4819010

hm1

• Allelic Composition: Pms2^tm1Lisk/Pms2^tm1Lisk
• Genetic Background: involves: 129S2/SvPas

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

mortality/aging

premature death ( J:125218 , J:162378 )

• median survival is reduced compared to in wild-type mice (J:125218)

• median survival is 13 months (J:162378)

reproductive system

teratozoospermia ( J:162378 )

♂ • mature sperm have misshapen heads and truncated or coiled flagella

coiled sperm flagellum ( J:162378 )

♂

short sperm flagellum ( J:162378 )

♂

abnormal sperm head morphology ( J:162378 )

♂

decreased male germ cell number ( J:162378 )

♂ • severe depletion of spermatogenic cells

abnormal seminiferous tubule morphology ( J:162378 )

♂ • severely depleted in spermatogenic cells

small testis ( J:162378 )

♂ • about 70% the size of wild-type testes

male infertility ( J:162378 )

♂

cellular

teratozoospermia ( J:162378 )

♂ • mature sperm have misshapen heads and truncated or coiled flagella

coiled sperm flagellum ( J:162378 )

♂

short sperm flagellum ( J:162378 )

♂

abnormal sperm head morphology ( J:162378 )

♂

decreased male germ cell number ( J:162378 )

♂ • severe depletion of spermatogenic cells

abnormal cell physiology ( J:125218 )

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

abnormal DNA repair ( J:162378 )

• increase in microsatellite instability and mutation frequencies

abnormal mismatch repair ( J:162378 )

• absence of MMR in MEFs

chromosomal instability ( J:125218 )

• mouse embryonic fibroblasts (MEFs) exhibit in increase in microsatellite instability compared with wild-type cells

• end-to-end chromosome fusions in MEFs are slightly increased compared to in wild-type cells

• MEFs exhibit an increase in chromosome breaks, fragments, bivalent recombination figures, chromatid cross-links, chromosome fusions, and minichromosomes compared with wild-type cells

• however, telomere length is normal

neoplasm

increased lymphoma incidence ( J:125218 )

increased B cell derived lymphoma incidence ( J:162378 )

increased carcinoma incidence ( J:125218 )

increased sarcoma incidence ( J:125218 )

• histiocytic sarcomas

immune system

abnormal class switch recombination ( J:162378 )

• decrease in ex vivo class switch recombination

hematopoietic system

abnormal class switch recombination ( J:162378 )

• decrease in ex vivo class switch recombination

homeostasis/metabolism

abnormal DNA repair ( J:162378 )

• increase in microsatellite instability and mutation frequencies

abnormal mismatch repair ( J:162378 )

• absence of MMR in MEFs

endocrine/exocrine glands

abnormal seminiferous tubule morphology ( J:162378 )

♂ • severely depleted in spermatogenic cells

small testis ( J:162378 )

♂ • about 70% the size of wild-type testes

Genotype
MGI:2663888

hm2

• Allelic Composition: Pms2^tm1Lisk/Pms2^tm1Lisk
• Genetic Background: involves: 129S2/SvPas * C57BL/6

neoplasm

increased lymphoma incidence ( J:27389 )

increased sarcoma incidence ( J:27389 )

reproductive system

abnormal sperm flagellum morphology ( J:27389 )

♂ • truncated, irregular flagella

oligozoospermia ( J:27389 )

♂ • spermatozoan content of the epididymis was <25% that of wild-type

globozoospermia ( J:27389 )

♂ • misshaped heads

abnormal male meiosis ( J:27389 )

♂ • abnormalities in chromosomal synapsis during meiotic prophase I

male infertility ( J:27389 )

♂ • female mice are fertile

cellular

abnormal sperm flagellum morphology ( J:27389 )

♂ • truncated, irregular flagella

oligozoospermia ( J:27389 )

♂ • spermatozoan content of the epididymis was <25% that of wild-type

globozoospermia ( J:27389 )

♂ • misshaped heads

abnormal male meiosis ( J:27389 )

♂ • abnormalities in chromosomal synapsis during meiotic prophase I

abnormal mismatch repair ( J:27389 )

• DNA from tumors and sperm exhibits increased microsatellite instability

homeostasis/metabolism

abnormal mismatch repair ( J:27389 )

• DNA from tumors and sperm exhibits increased microsatellite instability

Genotype
MGI:4820592

ht3

• Allelic Composition: Pms2^tm1Lisk/Pms2⁺
• Genetic Background: involves: 129S2/SvPas

neoplasm

increased incidence of tumors by chemical induction ( J:61787 )

• N-methyl-N-nitrosourea (MNU)-treated mice exhibit a higher incidence and multiplicity of intestinal tumors (adenomas and adenocarcinomas) compared with similarly treated wild-type mice without loss of the wild-type allele

• however, the incidence of induced thymic lymphomas is normal

homeostasis/metabolism

increased incidence of tumors by chemical induction ( J:61787 )

• N-methyl-N-nitrosourea (MNU)-treated mice exhibit a higher incidence and multiplicity of intestinal tumors (adenomas and adenocarcinomas) compared with similarly treated wild-type mice without loss of the wild-type allele

• however, the incidence of induced thymic lymphomas is normal

Genotype
MGI:4820641

cx4

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

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

Genotype
MGI:4820588

cx5

• Allelic Composition: Apc^Min/Apc⁺; Pms2^tm1Lisk/Pms2^tm1Lisk
• Genetic Background: involves: 129S2/SvPas * C57BL/6J

mortality/aging

premature death ( J:46419 )

• mice die earlier than Apc^min heterozygotes

neoplasm

increased intestinal adenoma incidence ( J:46419 )

• tumors exhibit microsatellite instability

• mice develop 2.3 times more adenomatous polyps in the intestine compared with Apc^min heterozygotes

• however, no evidence of adenocarcinoma is observed

digestive/alimentary system

intestine polyps ( J:46419 )

• mice develop 2.3 times more adenomatous polyps in the intestine compared with Apc^min heterozygotes

increased intestinal adenoma incidence ( J:46419 )

• mice develop 2.3 times more adenomatous polyps in the intestine compared with Apc^min heterozygotes

• however, no evidence of adenocarcinoma is observed

• tumors exhibit microsatellite instability