Phenotypes associated with this allele

• Allele Symbol: Smad4^tm1Mmt
• Allele Name: targeted mutation 1, Makoto M Taketo
• Allele ID: MGI:1857697
• Summary: 4 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Smad4^tm1Mmt/Smad4^tm1Mmt	involves: 129S2/SvPas * C57BL/6	MGI:2182800
ht2	Smad4^tm1Mmt/Smad4^+	B6.129S2-Smad4^tm1Mmt	MGI:2182801
cx3	Apc^tm1Mmt/Apc^+ Mmp7^tm1Lmm/Mmp7^tm1Lmm Smad4^tm1Mmt/Smad4^+	involves: 129S1/Sv * 129S2/SvPas * 129X1/SvJ	MGI:4365607
cx4	Apc^tm1Mmt/Apc^+ Smad4^tm1Mmt/Smad4^+	involves: 129S2/SvPas * C57BL/6	MGI:2182802

Genotype
MGI:2182800

hm1

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

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

mortality/aging

embryonic lethality between implantation and somite formation, complete penetrance ( J:46242 )

• embryos of normal appearance found only before 7 days post-coitum

Genotype
MGI:2182801

ht2

• Allelic Composition: Smad4^tm1Mmt/Smad4⁺
• Genetic Background: B6.129S2-Smad4^tm1Mmt

digestive/alimentary system

duodenum polyps ( J:59214 )

• mutants older than 1 year develop inflammatory polyps in the duodenum

gastric polyps ( J:59214 )

• mutants older than 1 year develop inflammatory polyps in the glandular stomach, often in the pyloric region

• polyps show Smad4 loss of heterozygosity

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
juvenile polyposis syndrome		DOID:0050787	OMIM:174900	J:59214

Genotype
MGI:4365607

cx3

• 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:2182802

cx4

• 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