Phenotypes Associated with This Genotype

Genotype
MGI:2663863

• Allelic Composition: Mlh1^tm1Rak/Mlh1^tm1Rak
• Genetic Background: involves: 129P2/OlaHsd * C57BL/6

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

mortality/aging

premature death ( J:53451 , J:98929 )

• 50% of mice die by 7 months (J:53451)

• early moridity in mice treated with DES (J:98929)

• death at 161-164 days in treated mice (J:98929)

• death at 297-299 days for untreated mice (J:98929)

reproductive system

azoospermia ( J:33878 )

♂

abnormal female meiosis ( J:33878 )

♀ • oocytes do not complete meiosis II

arrest of male meiosis ( J:33878 )

♂ • arrest at pachytene

small testis ( J:33878 )

♂

female infertility ( J:33878 )

♀

male infertility ( J:33878 )

♂

neoplasm

increased tumor incidence ( J:53451 )

• 72% of mice develop tumors

increased gastrointestinal tumor incidence ( J:53451 )

• 33% of mice develop gastrointestinal tumors in the stomach, duodenum, jejunum, ileum, and colon

increased adenoma incidence ( J:53451 )

• 50% of mice develop adenomas

increased lymphoma incidence ( J:53451 )

• some mice develop non-Hodgkin's lymphoma (5 of 8 T cell type, 2 of 8 B cell type) and Hodgkin's lymphoma

increased T cell derived lymphoma incidence ( J:53451 )

• 5 of 8

increased B cell derived lymphoma incidence ( J:53451 , J:98929 )

• 2 of 8 (J:53451)

• five of eight lymphomas tested are B cell lymphomas (J:98929)

increased carcinoma incidence ( J:53451 )

• mice develop 13% carcinomas and 37% early invasive carcinomas

• one mouse develops sweat gland carcinoma

cellular

azoospermia ( J:33878 )

♂

abnormal female meiosis ( J:33878 )

♀ • oocytes do not complete meiosis II

arrest of male meiosis ( J:33878 )

♂ • arrest at pachytene

abnormal apoptosis ( J:33878 )

• apoptosis of arrested germ cells

endocrine/exocrine glands

increased T cell derived lymphoma incidence ( J:53451 )

• 5 of 8

small testis ( J:33878 )

♂

digestive/alimentary system

increased gastrointestinal tumor incidence ( J:53451 )

• 33% of mice develop gastrointestinal tumors in the stomach, duodenum, jejunum, ileum, and colon

immune system

increased T cell derived lymphoma incidence ( J:53451 )

• 5 of 8

hematopoietic system

increased T cell derived lymphoma incidence ( J:53451 )

• 5 of 8

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
Lynch syndrome		DOID:3883	OMIM:PS120435	J:53451