Phenotypes associated with this allele

• Allele Symbol: Apc^tm1Mmt
• Allele Name: targeted mutation 1, Makoto M Taketo
• Allele ID: MGI:1857957
• Summary: 11 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Apc^tm1Mmt/Apc^tm1Mmt	involves: 129S2/SvPas * C57BL/6J	MGI:2175906
ht2	Apc^tm1Mmt/Apc^+	involves: 129S2/SvPas * C57BL/6J	MGI:2175907
cn3	Tle5^tm1.1Mmt/Tle5^tm1.1Mmt Apc^tm1Mmt/Apc^+ Tg(Vil1-cre/ERT2)23Syr/0	involves: 129S2/SvPas * C57BL/6 * DBA * SJL	MGI:4888016
cx4	Cdx2^tm1Mmt/Cdx2^+ Apc^tm1Mmt/Apc^+	B6.129-Cdx2^tm1Mmt Apc^tm1Mmt	MGI:3715020
cx5	Apc^tm1Mmt/Apc^+ Mmp7^tm1Lmm/Mmp7^tm1Lmm Smad4^tm1Mmt/Smad4^+	involves: 129S1/Sv * 129S2/SvPas * 129X1/SvJ	MGI:4365607
cx6	Apc^tm1Mmt/Apc^+ Smad2^tm2Kato/Smad2^+	involves: 129S2/SvPas * 129S4/SvJae * C57BL/6J	MGI:3790616
cx7	Apc^tm1Mmt/Apc^+ Smad2^tm1Kato/Smad2^+	involves: 129S2/SvPas * 129S4/SvJae * C57BL/6J	MGI:3790617
cx8	Apc^tm1Mmt/Apc^+ Ptgs2^tm1Jed/Ptgs2^+	involves: 129S2/SvPas * 129S7/SvEvBrd * C57BL/6J	MGI:3603949
cx9	Apc^tm1Mmt/Apc^+ Ptgs2^tm1Jed/Ptgs2^tm1Jed	involves: 129S2/SvPas * 129S7/SvEvBrd * C57BL/6J	MGI:3603950
cx10	Apc^tm1Mmt/Apc^+ Smad4^tm1Mmt/Smad4^+	involves: 129S2/SvPas * C57BL/6	MGI:2182802
cx11	Apc^tm1Mmt/Apc^+ Nkd1^tm1Tko/Nkd1^tm1Tko	involves: 129X1/SvJ	MGI:3531415

Genotype
MGI:2175906

hm1

• Allelic Composition: Apc^tm1Mmt/Apc^tm1Mmt
• Genetic Background: involves: 129S2/SvPas * C57BL/6J

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

mortality/aging

embryonic lethality between implantation and somite formation, incomplete penetrance ( J:25200 )

• most homozygous embryos die in utero prior to day 8 of gestation

Genotype
MGI:2175907

ht2

• Allelic Composition: Apc^tm1Mmt/Apc⁺
• Genetic Background: involves: 129S2/SvPas * C57BL/6J

Nascent intestinal polyps in Apc^tm1Mmt/Apc⁺ mice

neoplasm

increased intestinal adenoma incidence ( J:25200 , J:79668 )

• intestinal polyps are polyploid, papillary, or sessile adenoma; every polyp consists of a microadenoma covered with a normal layer of villous epithelium (J:25200)

• increase in incidence follows loss of normal Apc allele in nascent polyps (J:25200)

• numerous intestinal tumors develop in homozygotes (J:79668)

• most tumors are small; one animal developed a tumor >6 mm in diameter (J:79668)

digestive/alimentary system

increased intestinal adenoma incidence ( J:25200 , J:79668 )

• intestinal polyps are polyploid, papillary, or sessile adenoma; every polyp consists of a microadenoma covered with a normal layer of villous epithelium (J:25200)

• increase in incidence follows loss of normal Apc allele in nascent polyps (J:25200)

• numerous intestinal tumors develop in homozygotes (J:79668)

• most tumors are small; one animal developed a tumor >6 mm in diameter (J:79668)

intestine polyps ( J:79668 )

• multiple polyps develop soon after birth; all heterozygotes develop polyps by 7 weeks of age and numbers increase with age

• polyps are found from duodenum to rectum, mainly in small intestine

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
familial adenomatous polyposis		DOID:0050424	OMIM:PS175100	J:25200

Genotype
MGI:4888016

cn3

• Allelic Composition: Tle5^tm1.1Mmt/Tle5^tm1.1Mmt; Apc^tm1Mmt/Apc⁺; Tg(Vil1-cre/ERT2)23Syr/0
• Genetic Background: involves: 129S2/SvPas * C57BL/6 * DBA * SJL

neoplasm

increased colon adenocarcinoma incidence ( J:168065 )

• adenocarcinomas by histopathological definition

• the extent of cellular atypia and epithelial architecture are rather similar to those in the Apc^tm1Mmt adenomas, without a very malignant appearance

increased small intestine adenocarcinoma incidence ( J:168065 )

• adenocarcinomas by histopathological definition

• the extent of cellular atypia and epithelial architecture are rather similar to those in the Apc^tm1Mmt adenomas, without a very malignant appearance

increased metastatic potential ( J:168065 )

• treated with 4-hydroxytamoxifen to activate Cre recombinase at 3 weeks of age

• tumor invasion and intravasation into the smooth muscle layer of the small intestine and colon at 17 weeks of age

• in polyps larger than 2 mm in diameter, about half of them is found invading into the submucosa or beyond

• often seen inside vessels that are distended, reminiscent of tumor embolism

digestive/alimentary system

increased colon adenocarcinoma incidence ( J:168065 )

• adenocarcinomas by histopathological definition

• the extent of cellular atypia and epithelial architecture are rather similar to those in the Apc^tm1Mmt adenomas, without a very malignant appearance

increased small intestine adenocarcinoma incidence ( J:168065 )

• adenocarcinomas by histopathological definition

• the extent of cellular atypia and epithelial architecture are rather similar to those in the Apc^tm1Mmt adenomas, without a very malignant appearance

Genotype
MGI:3715020

cx4

• Allelic Composition: Cdx2^tm1Mmt/Cdx2⁺; Apc^tm1Mmt/Apc⁺
• Genetic Background: B6.129-Cdx2^tm1Mmt Apc^tm1Mmt

digestive/alimentary system

abnormal colon morphology ( J:86737 )

• increased anaphase bridge index

• accelerated transition from G1 to S phase

• increased DNA synthesis

• lower apoptotic rates

colon polyps ( J:86737 )

• increased in numbers relative to Apc^tm1Mmt

• mostly in the distal colon

abnormal small intestine morphology ( J:86737 )

• decreased anaphase bridge index

• decreased transition from G1 to S phase

• decreased DNA synthesis

• increased apoptotic rates

• significantly reduced number of polyps relative to Apc^tm1Mmt

cellular

abnormal chromosome morphology ( J:86737 )

• increased anaphase bridge index in the large intestine and decreased in the small intestine

abnormal cell cycle checkpoint function ( J:86737 )

• accelerated transition from G1 to S phase in the large intestine and decreased in the small intestine

• increased DNA synthesis in the large intestine and decreased in the small intestine

decreased apoptosis ( J:86737 )

• lower apoptotic rates in the large intestine

increased apoptosis ( J:86737 )

• in the small intestine

Genotype
MGI:4365607

cx5

• Allelic Composition: Apc^tm1Mmt/Apc⁺; Mmp7^tm1Lmm/Mmp7^tm1Lmm; Smad4^tm1Mmt/Smad4⁺
• Genetic Background: involves: 129S1/Sv * 129S2/SvPas * 129X1/SvJ

neoplasm

decreased tumor growth/size ( J:142797 )

• mice exhibit a decrease in tumors size compared to in Apc^tm1Mmt Smad4^tm1Mmt homozygotes

• the ratio of small tumors is increased compared to in Apc^tm1Mmt Smad4^tm1Mmt homozygotes

• however, mice exhibit the same tumor invasion depth and number of fibroblasts in tumor stroma as in Apc^tm1Mmt Smad4^tm1Mmt homozygotes

decreased tumor incidence ( J:142797 )

• mice develop 50% fewer tumors than in Apc^tm1Mmt Smad4^tm1Mmt homozygotes

Genotype
MGI:3790616

cx6

• Allelic Composition: Apc^tm1Mmt/Apc⁺; Smad2^tm2Kato/Smad2⁺
• Genetic Background: involves: 129S2/SvPas * 129S4/SvJae * C57BL/6J

mortality/aging

decreased tumor-free survival time ( J:79668 )

• a small number of mice die suddenly, before thirty weeks of age, as result of lethal intestinal obstruction by large tumorous polyps

neoplasm

increased intestinal adenoma incidence ( J:79668 )

• numerous intestinal tumors develop in homozygotes: compound mutants have more intestinal tumors >4 mm in diameter than Apc^tm1Mmt heterozygotes

• frequently one or two tumors >6 mm in diameter develop

• 10-15% of intestinal polyps exhibit stromal and vascular invasion

• tubular adenomas vary in size and shape, and solid colonies of poorly differentiated carcinoma cells are sometimes observed

• nuclei display more hyperchromaticity than those in tumors in Apc single heterozygotes; nuclear atypia in tumors is enhanced indicating increased malignancy

digestive/alimentary system

increased intestinal adenoma incidence ( J:79668 )

• numerous intestinal tumors develop in homozygotes: compound mutants have more intestinal tumors >4 mm in diameter than Apc^tm1Mmt heterozygotes

• frequently one or two tumors >6 mm in diameter develop

• 10-15% of intestinal polyps exhibit stromal and vascular invasion

• tubular adenomas vary in size and shape, and solid colonies of poorly differentiated carcinoma cells are sometimes observed

• nuclei display more hyperchromaticity than those in tumors in Apc single heterozygotes; nuclear atypia in tumors is enhanced indicating increased malignancy

Genotype
MGI:3790617

cx7

• Allelic Composition: Apc^tm1Mmt/Apc⁺; Smad2^tm1Kato/Smad2⁺
• Genetic Background: involves: 129S2/SvPas * 129S4/SvJae * C57BL/6J

mortality/aging

decreased tumor-free survival time ( J:79668 )

• a small number of mice die suddenly, before thirty weeks of age, as result of lethal intestinal obstruction by large tumorous polyps

neoplasm

increased intestinal adenoma incidence ( J:79668 )

• numerous intestinal tumors develop in homozygotes: compound mutants have more intestinal tumors >4 mm in diameter than Apc^tm1Mmt heterozygotes

• frequently one or two tumors >6 mm in diameter develop

• 10-15% of intestinal polyps exhibit stromal and vascular invasion

• tubular adenomas vary in size and shape, and solid colonies of poorly differentiated carcinoma cells are sometimes observed

• nuclei display more hyperchromaticity than those in tumors in Apc single heterozygotes; nuclear atypia in tumors is enhanced indicating increased malignancy

digestive/alimentary system

increased intestinal adenoma incidence ( J:79668 )

• numerous intestinal tumors develop in homozygotes: compound mutants have more intestinal tumors >4 mm in diameter than Apc^tm1Mmt heterozygotes

• frequently one or two tumors >6 mm in diameter develop

• 10-15% of intestinal polyps exhibit stromal and vascular invasion

• tubular adenomas vary in size and shape, and solid colonies of poorly differentiated carcinoma cells are sometimes observed

• nuclei display more hyperchromaticity than those in tumors in Apc single heterozygotes; nuclear atypia in tumors is enhanced indicating increased malignancy

Genotype
MGI:3603949

cx8

• Allelic Composition: Apc^tm1Mmt/Apc⁺; Ptgs2^tm1Jed/Ptgs2⁺
• Genetic Background: involves: 129S2/SvPas * 129S7/SvEvBrd * C57BL/6J

digestive/alimentary system

abnormal intestine morphology ( J:36816 )

• at 10 weeks, double heterozygotes develop only ~34% of the polyp number detected in the intestinal tracts of mice heterozygous for Apc^tm1Mmt alone

colon polyps ( J:36816 )

• at 10 weeks, double heterozygotes exhibit only 1.5 1.9 colonic polyps versus 6.8 7.2 detected in mice heterozygous for Apc^tm1Mmt alone

Genotype
MGI:3603950

cx9

• Allelic Composition: Apc^tm1Mmt/Apc⁺; Ptgs2^tm1Jed/Ptgs2^tm1Jed
• Genetic Background: involves: 129S2/SvPas * 129S7/SvEvBrd * C57BL/6J

digestive/alimentary system

abnormal intestine morphology ( J:36816 )

• at 10 weeks, these mutants develop only ~14% of the polyp number detected in the intestinal tracts of mice heterozygous for Apc^tm1Mmt alone

• the size of intestinal polyps is significantly smaller (<1.0 mm) than that observed in mice heterozygous for Apc^tm1Mmt alone, with no polyps larger than 2.0 mm in diameter

• histologically, well-developed polyps are not covered with the normal intestinal epithelium and appear flatter than polyps found in Apc^tm1Mmt heterozygous controls

• notably, no colonic polyps are observed

Genotype
MGI:2182802

cx10

• Allelic Composition: Apc^tm1Mmt/Apc⁺; Smad4^tm1Mmt/Smad4⁺
• Genetic Background: involves: 129S2/SvPas * C57BL/6

mortality/aging

premature death ( J:46242 )

• most mutants become moribund before 14-20 weeks and often die of intussusception of the small intestine

neoplasm

increased intestinal adenocarcinoma incidence ( J:46242 )

• polyps in small and large intestine develop into malignant adenocarcinomas, beginning at about 14 weeks

increased pancreatic ductal adenocarcinoma incidence ( J:46242 )

• adenocarcinomas found in ampullary region of the pancreatic duct, incomplete penetrance

integument

epidermal cyst ( J:46242 )

• in 53% of mice older than 10 weeks, skin epidermoid cysts found in left axillary region and/or ventral side of the neck

endocrine/exocrine glands

increased pancreatic ductal adenocarcinoma incidence ( J:46242 )

• adenocarcinomas found in ampullary region of the pancreatic duct, incomplete penetrance

growth/size/body

epidermal cyst ( J:46242 )

• in 53% of mice older than 10 weeks, skin epidermoid cysts found in left axillary region and/or ventral side of the neck

digestive/alimentary system

increased intestinal adenocarcinoma incidence ( J:46242 )

• polyps in small and large intestine develop into malignant adenocarcinomas, beginning at about 14 weeks

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
colorectal cancer		DOID:9256	OMIM:114500	J:46242

Genotype
MGI:3531415

cx11

• Allelic Composition: Apc^tm1Mmt/Apc⁺; Nkd1^tm1Tko/Nkd1^tm1Tko
• Genetic Background: involves: 129X1/SvJ

digestive/alimentary system

abnormal small intestine morphology ( J:95901 )

• the number and size distribution of small intestinal polyps is not different from mice heterozygous for Apc^tm1Mmt alone