Phenotypes associated with this allele

• Allele Symbol: Smad3⁺
• Allele Name: wild type
• Allele ID: MGI:1857591
• Summary: 10 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
ht1	Smad3^em1(IMPC)H/Smad3^+	C57BL/6NTac-Smad3^em1(IMPC)H/H	MGI:7415078
cn2	Smad2^tm1Rob/Smad2^tm2Rob Smad3^tm1Xfw/Smad3^+ Edil3^Tg(Sox2-cre)1Amc/Edil3^+	involves: 129/Sv * 129S/SvEv * C57BL/6 * CBA * CD-1	MGI:3689505
cx3	Rab25^tm1Jrgo/Rab25^tm1Jrgo Smad3^tm1Par/Smad3^+	129-Rab25^tm1Jrgo Smad3^tm1Par	MGI:4440865
cx4	Inha^tm1Bay/Inha^tm1Bay Smad3^tm1Par/Smad3^+	involves: 129S1/Sv * 129S7/SvEvBrd * 129X1/Sv * C57BL/6	MGI:3790432
cx5	Il6st^tm1Ern/Il6st^+ Smad3^tm1Par/Smad3^+	involves: 129S1/Sv * 129X1/SvJ * C57BL/6	MGI:3837663
cx6	Smad2^tm1Cxd/Smad2^+ Smad3^tm1Cxd/Smad3^+	involves: 129S6/SvEvTac * C57BL/6	MGI:3758897
cx7	Smad2^tm1Cxd/Smad2^+ Smad3^tm1Cxd/Smad3^+	involves: 129S6/SvEvTac * NIH Black Swiss	MGI:3758892
cx8	Nog^tm1Amc/Nog^+ Smad3^tm1Xfw/Smad3^+	involves: 129/Sv * 129S1/Sv	MGI:4819099
cx9	Nog^tm1Amc/Nog^tm1Amc Smad3^tm1Xfw/Smad3^+	involves: 129/Sv * 129S1/Sv	MGI:4819098
cx10	Chrd^tm1Emdr/Chrd^tm1Emdr Smad3^tm1Xfw/Smad3^+	involves: 129/Sv * 129S1/Sv * 129X1/SvJ	MGI:4819103

Genotype
MGI:7415078

ht1

• Allelic Composition: Smad3^em1(IMPC)H/Smad3⁺
• Genetic Background: C57BL/6NTac-Smad3^em1(IMPC)H/H

Data Sources

IMPC Data for Smad3

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

behavior/neurological

decreased exploration in new environment ( J:211773 )

♂

IMPC - HAR

hematopoietic system

decreased lymphocyte cell number ( J:211773 )

♀

IMPC - HAR

homeostasis/metabolism

decreased circulating alkaline phosphatase level ( J:211773 )

♀

IMPC - HAR

immune system

decreased lymphocyte cell number ( J:211773 )

♀

IMPC - HAR

Genotype
MGI:3689505

cn2

• Allelic Composition: Smad2^tm1Rob/Smad2^tm2Rob; Smad3^tm1Xfw/Smad3⁺; Edil3^{Tg(Sox2-cre)1Amc}/Edil3⁺
• Genetic Background: involves: 129/Sv * 129S/SvEv * C57BL/6 * CBA * CD-1

embryo

rostral body truncation ( J:84300 )

• embryos develop severe anterior truncations at E8.5

fused somites ( J:84300 )

• somites are fused across the midline at E8.5

digestive/alimentary system

absent foregut ( J:84300 )

• anterior gut is absent

cardiovascular system

abnormal heart development ( J:84300 )

• embryos develop heart malformations at E8.5

Genotype
MGI:4440865

cx3

• Allelic Composition: Rab25^tm1Jrgo/Rab25^tm1Jrgo; Smad3^tm1Par/Smad3⁺
• Genetic Background: 129-Rab25^tm1Jrgo Smad3^tm1Par

Colon tumor formation and neoplasia in Rab25^tm1Jrgo/Rab25^tm1Jrgo Smad3^tm1Par/Smad3⁺ mice

digestive/alimentary system

abnormal colon morphology ( J:158733 )

• the glandular atypia results in numerous mucin-filled cysts in one proximal colon tumor

colon polyps ( J:158733 )

• aberrant or dysplastic crypts, hyperplastic lesions, and adenomatous polyps

abnormal rectum morphology ( J:158733 )

• rectal tumor lesions in 80% of the mice

increased colon adenocarcinoma incidence ( J:158733 )

• large invasive tumor lesions in the proximal colonic mucosa in 80% of the mice

• the colonic epithelial tumors extend into and through the submucosa with neoplastic glands penetrating the muscle wall

neoplasm

increased colon adenocarcinoma incidence ( J:158733 )

• large invasive tumor lesions in the proximal colonic mucosa in 80% of the mice

• the colonic epithelial tumors extend into and through the submucosa with neoplastic glands penetrating the muscle wall

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
colorectal cancer		DOID:9256	OMIM:114500	J:158733

Genotype
MGI:3790432

cx4

• Allelic Composition: Inha^tm1Bay/Inha^tm1Bay; Smad3^tm1Par/Smad3⁺
• Genetic Background: involves: 129S1/Sv * 129S7/SvEvBrd * 129X1/Sv * C57BL/6

neoplasm

increased adrenal gland tumor incidence ( J:125349 )

• gonadectomy causes adrenal tumorigenesis which is dependent on the chronically elevated gonadotropin levels that result from this manipulation

• the 50% survival rate of female mice with gonadectomies is 37.5 weeks with all mice dying of extensive adrenal tumor burden

• this survival rate is significantly longer than in mice that are homozygote for Inha^tm1Bay but which have two wild-type alleles for Smad3

increased ovary tumor incidence ( J:125349 )

♀ • tumor mass is 50% less than in mice homozygote for Inha^tm1Bay but which have two wild-type alleles for Smad3

reproductive system

increased ovary tumor incidence ( J:125349 )

♀ • tumor mass is 50% less than in mice homozygote for Inha^tm1Bay but which have two wild-type alleles for Smad3

endocrine/exocrine glands

increased adrenal gland tumor incidence ( J:125349 )

• gonadectomy causes adrenal tumorigenesis which is dependent on the chronically elevated gonadotropin levels that result from this manipulation

• the 50% survival rate of female mice with gonadectomies is 37.5 weeks with all mice dying of extensive adrenal tumor burden

• this survival rate is significantly longer than in mice that are homozygote for Inha^tm1Bay but which have two wild-type alleles for Smad3

increased ovary tumor incidence ( J:125349 )

♀ • tumor mass is 50% less than in mice homozygote for Inha^tm1Bay but which have two wild-type alleles for Smad3

Genotype
MGI:3837663

cx5

• Allelic Composition: Il6st^tm1Ern/Il6st⁺; Smad3^tm1Par/Smad3⁺
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ * C57BL/6

neoplasm

increased adenoma incidence ( J:100160 )

• develop antral adenomas by 13-24 weeks of age

Genotype
MGI:3758897

cx6

• Allelic Composition: Smad2^tm1Cxd/Smad2⁺; Smad3^tm1Cxd/Smad3⁺
• Genetic Background: involves: 129S6/SvEvTac * C57BL/6

craniofacial

abnormal Meckel's cartilage morphology ( J:76396 )

• E11 mandibular explants cultured in vitro form thinner Meckel's cartilage and show a developmental delay

skeleton

abnormal Meckel's cartilage morphology ( J:76396 )

• E11 mandibular explants cultured in vitro form thinner Meckel's cartilage and show a developmental delay

Genotype
MGI:3758892

cx7

• Allelic Composition: Smad2^tm1Cxd/Smad2⁺; Smad3^tm1Cxd/Smad3⁺
• Genetic Background: involves: 129S6/SvEvTac * NIH Black Swiss

mortality/aging

lethality throughout fetal growth and development, complete penetrance ( J:106308 )

• lethality by E14.5 due to hepatic dysplasia

embryonic lethality during organogenesis, incomplete penetrance ( J:70388 )

• 10 of 21 E8.5-E10.5 mutants suffer lethality due to patterning defects

growth/size/body

embryonic growth retardation ( J:106308 )

• severely affected mutants are growth retarded at E9.5

increased fetal size ( J:70388 )

• E14.5 mutants are somewhat larger in size

liver/biliary system

abnormal hepatoblast migration ( J:106308 )

• marker analysis indicates defects in hepatoblast migration

abnormal liver morphology ( J:70388 )

• liver architecture is distorted

• cultured livers from E10.5 mutants do not exhibit outgrowth of liver lobules with primitive bile ducts as in wild-type, instead, they suffer extensive cell death or fail to develop normal liver architecture

dilated liver sinusoidal space ( J:70388 )

• dilated sinusoidal spaces

delayed hepatic development ( J:106308 )

• marker analysis indicates a delay in hepatogenesis

abnormal hepatic cord morphology ( J:70388 )

• arrangement of hepatocytes is abnormal in E14.5 livers; hepatocytes are found in small clusters and cell plates are absent unlike in wild-type where cords of hepatocytes are distributed throughout in the parenchyma

small liver ( J:70388 )

• small livers but have the correct number of lobes and appear red

liver hypoplasia ( J:70388 , J:106308 )

• 100% of E14.5 mutants exhibit severe liver hypoplasia (J:70388)

• liver is reduced in some mutants at E12.5-E14.5 (J:106308)

abnormal hepatocyte physiology ( J:70388 )

• hepatocytes cultured in vitro fail to adhere well to various substrates, expression of beta1 integrin is lost, and E-cadherin is mislocalized, indicating that hepatocytes have abnormal adhesive properties

decreased hepatocyte proliferation ( J:70388 )

• liver cells are in a less proliferative state than in wild-type as indicated by PCNA antibody staining

hematopoietic system

increased erythrocyte cell number ( J:70388 )

• increase in the number of erythrocytes in E14.5 livers

craniofacial

abnormal craniofacial morphology ( J:70388 , J:106308 )

• 20% of E14.5 mutants exhibit craniofacial defects in addition to the liver hypoplaisa (J:70388)

• some embryos display craniofacial defects as early as E8.5 (J:106308)

cardiovascular system

dilated liver sinusoidal space ( J:70388 )

• dilated sinusoidal spaces

abnormal heart looping ( J:106308 )

• some embryos exhibit abnormal heart looping

abnormal pericardial cavity morphology ( J:106308 )

• some embryos exhibit an enlarged pericardiac cavity

digestive/alimentary system

abnormal foregut morphology ( J:106308 )

• anterior ventral foregut defects at E8.5 as indicated by marker analysis, showing that the definitive endoderm fails to displace the visceral endoderm at the anterior intestinal portal

embryo

abnormal developmental patterning ( J:106308 )

• 54 of 106 mutants display patterning abnormalities of varying severity at E9.5-E10.5

• some embryos display midline defects as early as E8.5

abnormal gastrulation ( J:106308 )

• gastrulation defects

abnormal endoderm development ( J:106308 )

• definitive endoderm is reduced at E8.5 as indicated by marker analysis

• mutants display defects in the specification of hepatogenic endoderm

embryonic growth retardation ( J:106308 )

• severely affected mutants are growth retarded at E9.5

abnormal somite development ( J:106308 )

• severely affected mutants exhibit irregular somites at E9.5

endocrine/exocrine glands

small thyroid gland ( J:106308 )

• reduced thyroid at E10.5

nervous system

holoprosencephaly ( J:106308 )

• seen in some mutants

vision/eye

cyclopia ( J:106308 )

• seen in some mutants

cellular

abnormal hepatoblast migration ( J:106308 )

• marker analysis indicates defects in hepatoblast migration

decreased hepatocyte proliferation ( J:70388 )

• liver cells are in a less proliferative state than in wild-type as indicated by PCNA antibody staining

Genotype
MGI:4819099

cx8

• Allelic Composition: Nog^tm1Amc/Nog⁺; Smad3^tm1Xfw/Smad3⁺
• Genetic Background: involves: 129/Sv * 129S1/Sv

embryo

abnormal embryonic tissue morphology ( J:161524 )

• 5% (3 of 61) show defects in anterior midline tissues

Genotype
MGI:4819098

cx9

• Allelic Composition: Nog^tm1Amc/Nog^tm1Amc; Smad3^tm1Xfw/Smad3⁺
• Genetic Background: involves: 129/Sv * 129S1/Sv

nervous system

holoprosencephaly ( J:161524 )

• in 29% of mice

embryo

abnormal mesendoderm development ( J:161524 )

• expression analysis indicates defects in patterning and function in the anterior most axial mesendoderm

abnormal embryonic tissue morphology ( J:161524 )

• 29% (17 of 58) show defects in anterior midline tissues

abnormal anterior definitive endoderm morphology ( J:161524 )

• expression analysis indicates impairment in ADE specification

abnormal prechordal plate morphology ( J:161524 )

• expression analysis indicates defects in patterning and function

abnormal primitive streak formation ( J:161524 )

• expression analysis indicates a defect in anterior primitive streak development

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
holoprosencephaly		DOID:4621	OMIM:PS236100	J:161524

Genotype
MGI:4819103

cx10

• Allelic Composition: Chrd^tm1Emdr/Chrd^tm1Emdr; Smad3^tm1Xfw/Smad3⁺
• Genetic Background: involves: 129/Sv * 129S1/Sv * 129X1/SvJ

embryo

embryo phenotype ( J:161524 )

N • no defects are detected in anterior midline tissues