All Phenotypes Mlh1<tm1Rak> MGI Mouse

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Phenotypes associated with this allele

Allele Symbol
Allele Name
Allele ID

Mlh1^tm1Rak
targeted mutation 1, Raju Kucherlapati
MGI:1858054

Summary

9 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Mlh1^tm1Rak/Mlh1^tm1Rak	involves: 129P2/OlaHsd	MGI:3783420
hm2	Mlh1^tm1Rak/Mlh1^tm1Rak	involves: 129P2/OlaHsd * C57BL/6	MGI:2663863
hm3	Mlh1^tm1Rak/Mlh1^tm1Rak	involves: 129P2/OlaHsd * C57BL/6 * C57BL/6J	MGI:4366921
ht4	Mlh1^tm1Rak/Mlh1⁺	involves: 129P2/OlaHsd * C57BL/6	MGI:4412023
cx5	Mlh1^tm1Rak/Mlh1^tm1Rak Pole^tm1.1Bdp/Pole^tm1.1Bdp	involves: 129P2/OlaHsd * 129S1/Sv * 129X1/SvJ * C57BL/6 * C57BL/6J	MGI:4366924
cx6	Mlh1^tm1Rak/Mlh1^tm1Rak Pold1^tm1.1Bdp/Pold1^tm1.1Bdp	involves: 129P2/OlaHsd * 129S1/Sv * 129X1/SvJ * C57BL/6 * C57BL/6J	MGI:4366923
cx7	Fan1^em1Mem/Fan1^em1Mem Htt^tm5Mem/Htt⁺ Mlh1^tm1Rak/Mlh1^tm1Rak	involves: 129P2/OlaHsd * 129S1/Sv * 129X1/SvJ * C57BL/6J	MGI:6489857
cx8	Apc^tm1Rak/Apc⁺ Mlh1^tm1Rak/Mlh1⁺	involves: 129P2/OlaHsd * C57BL/6	MGI:4412022
cx9	Apc^tm1Rak/Apc⁺ Mlh1^tm1Rak/Mlh1^tm1Rak	involves: 129P2/OlaHsd * C57BL/6	MGI:4412021

Allelic Composition	Mlh1^tm1Rak/Mlh1^tm1Rak
Genetic Background	involves: 129P2/OlaHsd

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Mlh1^tm1Rak mutation (1 available); any Mlh1 mutation (44 available)

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

mortality/aging

premature death ( J:133352 )

• 50% of mice die by 30 weeks of age and all mice are dead by 64 weeks of age

neoplasm

increased gastrointestinal tumor incidence ( J:133352 )

• 35 mice exhibit small intestine tumors (19 of 31 are adenocarcinomas and 12 are adenomas)

• 8 of 66 mice exhibited both lymphomas and intestinal tumor

increased small intestine adenocarcinoma incidence ( J:133352 )

increased skin tumor incidence ( J:133352 )

• 4 of 66 mice develop squamous basal cell carcinoma of the skin

increased lymphoma incidence ( J:133352 )

• 35 of 66 mice develop T and B cell lymphomas

• 8 of 66 mice exhibited both lymphomas and intestinal tumor

homeostasis/metabolism

decreased physiological sensitivity to xenobiotic ( J:133352 )

• mouse embryonic fibroblasts are resistant to the effects of cisplatin unlike wild-type cells and exhibit a disruption of cell cycle arrest and reduced apoptosis following exposure

cellular

decreased sensitivity to induced cell death ( J:133352 )

• mouse embryonic fibroblasts are resistant to the effects of cisplatin unlike wild-type cells and exhibit a disruption of cell cycle arrest and reduced apoptosis following exposure

integument

increased skin tumor incidence ( J:133352 )

• 4 of 66 mice develop squamous basal cell carcinoma of the skin

digestive/alimentary system

increased gastrointestinal tumor incidence ( J:133352 )

• 35 mice exhibit small intestine tumors (19 of 31 are adenocarcinomas and 12 are adenomas)

• 8 of 66 mice exhibited both lymphomas and intestinal tumor

increased small intestine adenocarcinoma incidence ( J:133352 )

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

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Mlh1^tm1Rak mutation (1 available); any Mlh1 mutation (44 available)

♀	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

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

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Mlh1^tm1Rak mutation (1 available); any Mlh1 mutation (44 available)

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

mortality/aging

premature death ( J:153684 )

• mice die before 15 months

neoplasm

increased intestinal adenocarcinoma incidence ( J:153684 )

• 42% of mice develop intestinal adenomas and adenocarcinomas compared with 5% of wild-type mice

increased intestinal adenoma incidence ( J:153684 )

• 42% of mice develop intestinal adenomas and adenocarcinomas compared with 5% of wild-type mice

increased lymphoma incidence ( J:153684 )

• 4% of mice develop nodal lymphomas and 31% of mice develop follicular lymphomas

increased T cell derived lymphoma incidence ( J:153684 )

• in 38% of mice unlike wild-type mice

endocrine/exocrine glands

increased T cell derived lymphoma incidence ( J:153684 )

• in 38% of mice unlike wild-type mice

digestive/alimentary system

increased intestinal adenocarcinoma incidence ( J:153684 )

• 42% of mice develop intestinal adenomas and adenocarcinomas compared with 5% of wild-type mice

increased intestinal adenoma incidence ( J:153684 )

• 42% of mice develop intestinal adenomas and adenocarcinomas compared with 5% of wild-type mice

immune system

increased T cell derived lymphoma incidence ( J:153684 )

• in 38% of mice unlike wild-type mice

hematopoietic system

increased T cell derived lymphoma incidence ( J:153684 )

• in 38% of mice unlike wild-type mice

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

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Mlh1^tm1Rak mutation (1 available); any Mlh1 mutation (44 available)

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

mortality/aging

premature death ( J:53451 )

• 50% of mice die by 18 months

neoplasm

increased tumor incidence ( J:53451 )

• 32% of mice develop tumors at an average age of 9.8 months

increased gastrointestinal tumor incidence ( J:53451 )

• 14% of mice develop gastrointestinal tumors in the duodenum, jejunum, and colon

• mice develop an equal number of gastrointestinal tract adenocarcinomas and early invasive carcinoma

increased lymphoma incidence ( J:53451 )

• non-Hodgkin's lymphoma in one mouse

increased T cell derived lymphoma incidence ( J:53451 )

• in one mouse

increased carcinoma incidence ( J:53451 )

• mice develop an equal number of gastrointestinal tract adenocarcinomas and early invasive carcinoma

• mice develop sweat gland carcinoma

increased adenocarcinoma incidence ( J:53451 )

• mice develop an equal number of gastrointestinal tract adenocarcinomas and early invasive carcinoma

increased lung carcinoma incidence ( J:53451 )

• one mouse develops lung bronchio-alveolar carcinoma

increased squamous cell carcinoma incidence ( J:53451 )

• in the cervix of two mice

digestive/alimentary system

increased gastrointestinal tumor incidence ( J:53451 )

• 14% of mice develop gastrointestinal tumors in the duodenum, jejunum, and colon

• mice develop an equal number of gastrointestinal tract adenocarcinomas and early invasive carcinoma

respiratory system

increased lung carcinoma incidence ( J:53451 )

• one mouse develops lung bronchio-alveolar carcinoma

endocrine/exocrine glands

increased T cell derived lymphoma incidence ( J:53451 )

• in one mouse

hematopoietic system

increased T cell derived lymphoma incidence ( J:53451 )

• in one mouse

immune system

increased T cell derived lymphoma incidence ( J:53451 )

• in one mouse

Allelic Composition	Mlh1^tm1Rak/Mlh1^tm1Rak Pole^tm1.1Bdp/Pole^tm1.1Bdp
Genetic Background	involves: 129P2/OlaHsd * 129S1/Sv * 129X1/SvJ * C57BL/6 * C57BL/6J

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Mlh1^tm1Rak mutation (1 available); any Mlh1 mutation (44 available)
Pole^tm1.1Bdp mutation (0 available); any Pole mutation (102 available)

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

mortality/aging

lethality during fetal growth through weaning, complete penetrance ( J:153684 )

• mice are present in normal ratios up to E14.5; none are recovered at weaning

Allelic Composition	Mlh1^tm1Rak/Mlh1^tm1Rak Pold1^tm1.1Bdp/Pold1^tm1.1Bdp
Genetic Background	involves: 129P2/OlaHsd * 129S1/Sv * 129X1/SvJ * C57BL/6 * C57BL/6J

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Mlh1^tm1Rak mutation (1 available); any Mlh1 mutation (44 available)
Pold1^tm1.1Bdp mutation (0 available); any Pold1 mutation (64 available)

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

mortality/aging

embryonic lethality during organogenesis, complete penetrance ( J:153684 )

• mice do not survive beyond E9.5

Allelic Composition	Fan1^em1Mem/Fan1^em1Mem Htt^tm5Mem/Htt⁺ Mlh1^tm1Rak/Mlh1^tm1Rak
Genetic Background	involves: 129P2/OlaHsd * 129S1/Sv * 129X1/SvJ * C57BL/6J

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Fan1^em1Mem mutation (0 available); any Fan1 mutation (99 available)
Htt^tm5Mem mutation (2 available); any Htt mutation (178 available)
Mlh1^tm1Rak mutation (1 available); any Mlh1 mutation (44 available)

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

cellular

cellular phenotype ( J:298297 )

N	• Htt CAG repeat stability is normal

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

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Apc^tm1Rak mutation (1 available); any Apc mutation (158 available)
Mlh1^tm1Rak mutation (1 available); any Mlh1 mutation (44 available)

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

mortality/aging

premature death ( J:53451 )

• all mice die by 14 months of age

neoplasm

increased tumor incidence ( J:53451 )

• 85% of mice develop tumors at an average age of 9.4 months

• 77% of mice develop gastrointestinal tract tumors and 23% of mice develop extra-gastrointestinal tract tumors

increased gastrointestinal tumor incidence ( J:53451 )

• 77% of mice develop gastrointestinal tract tumors

• mice exhibit a 7-fold increase in gastrointestinal tumors compared to Mlh1^tm1Rak heterozygotes

digestive/alimentary system

increased gastrointestinal tumor incidence ( J:53451 )

• 77% of mice develop gastrointestinal tract tumors

• mice exhibit a 7-fold increase in gastrointestinal tumors compared to Mlh1^tm1Rak heterozygotes

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

Find Mice

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

mortality/aging

premature death ( J:53451 )

• all mice die by 4 months of age

neoplasm

increased tumor incidence ( J:53451 )

• all mice develop tumors at an average age of 3.3 months

• all mice develop gastrointestinal tract tumors and 9% develop non-gastrointestinal tract tumors

increased gastrointestinal tumor incidence ( J:53451 )

• all mice develop gastrointestinal tract tumors

• mice exhibit a 30-fold increase in gastrointestinal tumors compared to Mlh1^tm1Rak homozygotes

• mice exhibit a 4- to 5-fold increase in stomach and colon tumors, and a 25- to 100-fold increase in duodenum, jejunum, and ileum compared to in homozygous mice

increased skin tumor incidence ( J:53451 )

• one mouse develops skin carcinoma with lung metastasis

increased adenoma incidence ( J:53451 )

• 34% of mice develop microadenomas and 36% adenomas

increased lymphoma incidence ( J:53451 )

• non-Hodgkin's lymphoma in two mice

increased carcinoma incidence ( J:53451 )

• mice develop gastrointestinal adenocarcinomas, early invasive carcinomas (in 13% of mice), and carcinomas (in 17% of mice)

increased adenocarcinoma incidence ( J:53451 )

digestive/alimentary system

melena ( J:53451 )

• at 2 to 4 weeks of age

increased gastrointestinal tumor incidence ( J:53451 )

• all mice develop gastrointestinal tract tumors

• mice exhibit a 30-fold increase in gastrointestinal tumors compared to Mlh1^tm1Rak homozygotes

• mice exhibit a 4- to 5-fold increase in stomach and colon tumors, and a 25- to 100-fold increase in duodenum, jejunum, and ileum compared to in homozygous mice

integument

increased skin tumor incidence ( J:53451 )

• one mouse develops skin carcinoma with lung metastasis

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

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