Mouse Genome Informatics
hm1
    Mlh1tm1Rak/Mlh1tm1Rak
involves: 129P2/OlaHsd
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• 50% of mice die by 30 weeks of age and all mice are dead by 64 weeks of age

tumorigenesis
• 4 of 66 mice develop squamous basal cell carcinoma of the skin
• 35 of 66 mice develop T and B cell lymphomas
• 8 of 66 mice exhibited both lymphomas and intestinal tumor
• 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

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


Mouse Genome Informatics
hm2
    Mlh1tm1Rak/Mlh1tm1Rak
involves: 129P2/OlaHsd * C57BL/6
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• 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
(J:33878)
(J:33878)
• oocytes do not complete meiosis II (J:33878)
• arrest at pachytene (J:33878)
(J:33878)

tumorigenesis
• 72% of mice develop tumors
• 50% of mice develop adenomas
• some mice develop non-Hodgkin's lymphoma (5 of 8 T cell type, 2 of 8 B cell type) and Hodgkin's lymphoma
• 2 of 8 (J:53451)
• five of eight lymphomas tested are B cell lymphomas (J:98929)
• mice develop 13% carcinomas and 37% early invasive carcinomas
• one mouse develops sweat gland carcinoma
• 33% of mice develop gastrointestinal tumors in the stomach, duodenum, jejunum, ileum, and colon

cellular
• apoptosis of arrested germ cells

endocrine/exocrine glands
(J:33878)

Mouse Models of Human Disease
OMIM IDRef(s)
Colorectal Cancer, Hereditary Nonpolyposis, Type 2; HNPCC2 609310 J:53451


Mouse Genome Informatics
hm3
    Mlh1tm1Rak/Mlh1tm1Rak
involves: 129P2/OlaHsd * C57BL/6 * C57BL/6J
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• mice die before 15 months

tumorigenesis
• 42% of mice develop intestinal adenomas and adenocarcinomas compared with 5% of wild-type mice
• 4% of mice develop nodal lymphomas and 31% of mice develop follicular lymphomas
• in 38% of mice unlike wild-type mice
• 42% of mice develop intestinal adenomas and adenocarcinomas compared with 5% of wild-type mice


Mouse Genome Informatics
ht4
    Mlh1tm1Rak/Mlh1+
involves: 129P2/OlaHsd * C57BL/6
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• 50% of mice die by 18 months

tumorigenesis
• 32% of mice develop tumors at an average age of 9.8 months
• non-Hodgkin's lymphoma in one mouse
• mice develop an equal number of gastrointestinal tract adenocarcinomas and early invasive carcinoma
• mice develop sweat gland carcinoma
• mice develop an equal number of gastrointestinal tract adenocarcinomas and early invasive carcinoma
• one mouse develops lung bronchio-alveolar carcinoma
• in the cervix of two mice
• 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


Mouse Genome Informatics
cx5
    Mlh1tm1Rak/Mlh1tm1Rak
Pold1tm1.1Bdp/Pold1tm1.1Bdp

involves: 129P2/OlaHsd * 129S1/Sv * 129X1/SvJ * C57BL/6 * C57BL/6J
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• mice do not survive beyond E9.5


Mouse Genome Informatics
cx6
    Mlh1tm1Rak/Mlh1tm1Rak
Poletm1.1Bdp/Poletm1.1Bdp

involves: 129P2/OlaHsd * 129S1/Sv * 129X1/SvJ * C57BL/6 * C57BL/6J
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• mice are present in normal ratios up to E14.5; none are recovered at weaning


Mouse Genome Informatics
cx7
    Apctm1Rak/Apc+
Mlh1tm1Rak/Mlh1tm1Rak

involves: 129P2/OlaHsd * C57BL/6
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• all mice die by 4 months of age

tumorigenesis
• 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
• one mouse develops skin carcinoma with lung metastasis
• 34% of mice develop microadenomas and 36% adenomas
• non-Hodgkin's lymphoma in two mice
• mice develop gastrointestinal adenocarcinomas, early invasive carcinomas (in 13% of mice), and carcinomas (in 17% of mice)
• all mice develop gastrointestinal tract tumors
• mice exhibit a 30-fold increase in gastrointestinal tumors compared to Mlh1tm1Rak 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

digestive/alimentary system
• at 2 to 4 weeks of age

integument
• one mouse develops skin carcinoma with lung metastasis

Mouse Models of Human Disease
OMIM IDRef(s)
Colorectal Cancer, Hereditary Nonpolyposis, Type 2; HNPCC2 609310 J:53451


Mouse Genome Informatics
cx8
    Apctm1Rak/Apc+
Mlh1tm1Rak/Mlh1+

involves: 129P2/OlaHsd * C57BL/6
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• all mice die by 14 months of age

tumorigenesis
• 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
• 77% of mice develop gastrointestinal tract tumors
• mice exhibit a 7-fold increase in gastrointestinal tumors compared to Mlh1tm1Rak heterozygotes