All Phenotypes Smad4<tm2.1Cxd> MGI Mouse

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Phenotypes associated with this allele

Allele Symbol
Allele Name
Allele ID

Smad4^tm2.1Cxd
targeted mutation 2.1, Chu-Xia Deng
MGI:2386393

Summary

21 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
cn1	Smad4^tm2.1Cxd/Smad4^tm2.1Cxd Tg(Foxn1-cre)8Ghr/0	B6.Cg-Smad4^tm2.1Cxd Tg(Foxn1-cre)8Ghr	MGI:3810117
cn2	Cdh1^tm2Kem/Cdh1⁺ Smad4^tm2.1Cxd/Smad4^tm2.1Cxd Trp53^tm1Brn/Trp53^tm1Brn Tg(Vil1-cre)20Syr/0	involves: 129 * C57BL/6 * DBA/2	MGI:5634401
cn3	Cdh1^tm2Kem/Cdh1⁺ Smad4^tm2.1Cxd/Smad4^tm2.1Cxd Trp53^tm1Brn/Trp53^tm1Brn Tg(Pdx1-cre)6Tuv/0	involves: 129 * C57BL/6 * FVB/N	MGI:5634400
cn4	Cdh1^tm2Kem/Cdh1^tm2Kem Smad4^tm2.1Cxd/Smad4^tm2.1Cxd Trp53^tm1Brn/Trp53^tm1Brn Tg(Pdx1-cre)6Tuv/0	involves: 129 * C57BL/6 * FVB/N	MGI:5634407
cn5	Cdh1^tm2Kem/Cdh1⁺ Smad4^tm2.1Cxd/Smad4^tm2.1Cxd Trp53^tm1Brn/Trp53^tm1Brn Tg(MMTV-cre)7Mul/0	involves: 129 * C57BL/6 * FVB/N	MGI:5634403
cn6	Pten^tm2Mak/Pten^tm2Mak Smad4^tm2.1Cxd/Smad4^tm2.1Cxd Tg(KRT5-cre)1Xya/0	involves: 129P2/OlaHsd * 129S6/SvEvTac	MGI:3607778
cn7	Smad4^tm2.1Cxd/Smad4^tm2.1Cxd Trp53^tm1Brn/Trp53^tm1Brn Tg(Vil1-cre)20Syr/0	involves: 129P2/OlaHsd * 129S6/SvEvTac * C57BL/6 * DBA/2	MGI:5634402
cn8	Smad4^tm2.1Cxd/Smad4^tm2.1Cxd Trp53^tm1Brn/Trp53^tm1Brn Tg(Pdx1-cre)6Tuv/0	involves: 129P2/OlaHsd * 129S6/SvEvTac * C57BL/6 * FVB/N	MGI:5634408
cn9	Smad4^tm2.1Cxd/Smad4^tm2.1Cxd Trp53^tm1Brn/Trp53^tm1Brn Tg(MMTV-cre)7Mul/0	involves: 129P2/OlaHsd * 129S6/SvEvTac * FVB/N	MGI:5634404
cn10	Smad4^tm2.1Cxd/Smad4^tm2.1Cxd Kdr^tm1(cre)Sato/Kdr⁺	involves: 129S1/Sv * 129S6/SvEvTac	MGI:3687383
cn11	Kras^tm4Tyj/Kras⁺ Smad4^tm2.1Cxd/Smad4^tm2.1Cxd Tg(Krt1-15-cre/PGR*)22Cot/0	involves: 129S4/SvJae * 129S6/SvEvTac * C57BL/6 * C57BL/6J * SJL/J	MGI:5556259
cn12	Pten^tm1Hwu/Pten^tm1Hwu Smad4^tm2.1Cxd/Smad4^tm2.1Cxd Tg(Alb1-cre)1Dlr/0	involves: 129S4/SvJae * 129S6/SvEvTac * FVB/N	MGI:4839217
cn13	Smad4^tm2.1Cxd/Smad4^tm2.1Cxd Tg(KRT5-cre)1Xya/0	involves: 129S6/SvEvTac	MGI:3607725
cn14	Smad4^tm2.1Cxd/Smad4^tm2.1Cxd Tg(Pou5f1-cre/ERT2)#Ysa/0	involves: 129S6/SvEvTac	MGI:5615472
cn15	Smad4^tm2.1Cxd/Smad4^tm2.1Cxd Tg(ACTA1-cre)AMcle/0	involves: 129S6/SvEvTac * C57BL/6	MGI:5297811
cn16	Smad4^tm2.1Cxd/Smad4^tm2.1Cxd Tg(Krt1-15-cre/PGR*)22Cot/0	involves: 129S6/SvEvTac * C57BL/6 * C57BL/6J * SJL/J	MGI:5556247
cn17	Smad4^tm2.1Cxd/Smad4^tm2.1Cxd Tg(Dppa3-cre/Esr1*)3Sait/0	involves: 129S6/SvEvTac * C57BL/6 * DBA	MGI:5462061
cn18	Smad4^tm2.1Cxd/Smad4^tm2.1Cxd Tg(Sp7-tTA,tetO-EGFP/cre)1Amc/0	involves: 129S6/SvEvTac * C57BL/6J * CD-1	MGI:5604139
cn19	Smad4^tm2.1Cxd/Smad4⁺ Tg(Sp7-tTA,tetO-EGFP/cre)1Amc/0	involves: 129S6/SvEvTac * C57BL/6J * CD-1	MGI:5604140
cn20	Smad4^tm2.1Cxd/Smad4^tm2.1Cxd Tg(Capn8-cre)1Xya/0	involves: 129S6/SvEvTac * FVB/N	MGI:4365917
cn21	Smad4^tm2.1Cxd/Smad4^tm2.1Cxd Tg(Nes-cre)1Atp/0	involves: 129S6/SvEvTac * FVB/N	MGI:3608993

Allelic Composition	Smad4^tm2.1Cxd/Smad4^tm2.1Cxd Tg(Foxn1-cre)8Ghr/0
Genetic Background	B6.Cg-Smad4^tm2.1Cxd Tg(Foxn1-cre)8Ghr

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Smad4^tm2.1Cxd mutation (2 available); any Smad4 mutation (43 available)
Tg(Foxn1-cre)8Ghr mutation (0 available)

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

immune system

small thymus ( J:138837 )

• mice exhibit small thymus

• however, the cellularity and histology of the thymus are normal

abnormal thymus physiology ( J:138837 )

• unlike in wild type mice, the thymus is resistant to increased cellularity induced by KGF

hematopoietic system

small thymus ( J:138837 )

• mice exhibit small thymus

• however, the cellularity and histology of the thymus are normal

abnormal thymus physiology ( J:138837 )

• unlike in wild type mice, the thymus is resistant to increased cellularity induced by KGF

endocrine/exocrine glands

small thymus ( J:138837 )

• mice exhibit small thymus

• however, the cellularity and histology of the thymus are normal

abnormal thymus physiology ( J:138837 )

• unlike in wild type mice, the thymus is resistant to increased cellularity induced by KGF

Allelic Composition	Cdh1^tm2Kem/Cdh1⁺ Smad4^tm2.1Cxd/Smad4^tm2.1Cxd Trp53^tm1Brn/Trp53^tm1Brn Tg(Vil1-cre)20Syr/0
Genetic Background	involves: 129 * C57BL/6 * DBA/2

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Cdh1^tm2Kem mutation (1 available); any Cdh1 mutation (171 available)
Smad4^tm2.1Cxd mutation (2 available); any Smad4 mutation (43 available)
Tg(Vil1-cre)20Syr mutation (3 available)
Trp53^tm1Brn mutation (18 available); any Trp53 mutation (232 available)

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

neoplasm

increased intestinal adenocarcinoma incidence ( J:212549 )

• mice develop intestinal adenocarcinomas with a median tumor-free survival of 5.2 months of age and no distant metastases are seen

digestive/alimentary system

increased intestinal adenocarcinoma incidence ( J:212549 )

• mice develop intestinal adenocarcinomas with a median tumor-free survival of 5.2 months of age and no distant metastases are seen

Allelic Composition	Cdh1^tm2Kem/Cdh1⁺ Smad4^tm2.1Cxd/Smad4^tm2.1Cxd Trp53^tm1Brn/Trp53^tm1Brn Tg(Pdx1-cre)6Tuv/0
Genetic Background	involves: 129 * C57BL/6 * FVB/N

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Cdh1^tm2Kem mutation (1 available); any Cdh1 mutation (171 available)
Smad4^tm2.1Cxd mutation (2 available); any Smad4 mutation (43 available)
Tg(Pdx1-cre)6Tuv mutation (3 available)
Trp53^tm1Brn mutation (18 available); any Trp53 mutation (232 available)

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

mortality/aging

premature death ( J:212549 )

• most common cause of death is duodenal obstruction, followed by gastric outlet obstruction

neoplasm

increased duodenum adenocarcinoma incidence ( J:212549 )

• 36% of mice develop duodenal adenocarcinomas

increased gastric adenocarcinoma incidence ( J:212549 )

• 84% of mice develop spontaneous tumors in the glandular stomach with a median tumor-free survival of 8 months

• gastric tumors resemble diffuse-type gastric adenocarcinomas, are E-cadherin-negative, and are invasive into the muscle layers and regional lymph nodes

• intramucosal adenocarcinomas with signet ring cell feature is seen in 2 of 4 mice at 6 months of age

• gastric premalignant lesions such as atrophic gastritis, metaplasia or dysplasia are not seen at 4 and 5 months of age

increased metastatic potential ( J:212549 )

• 3 of 21 mice with gastric adenocarcinomas develop lung metastases

• metastatic lesions have similar cytologic features to primary gastric tumors

• 8% of mice exhibit adenocarcinomas in the pancreas, most likely due to invasion of the primary duodenal or gastric adenocarcinomas

increased squamous cell carcinoma incidence ( J:212549 )

• 24% of mice develop forestomach squamous cell carcinomas

digestive/alimentary system

increased duodenum adenocarcinoma incidence ( J:212549 )

• 36% of mice develop duodenal adenocarcinomas

increased gastric adenocarcinoma incidence ( J:212549 )

• 84% of mice develop spontaneous tumors in the glandular stomach with a median tumor-free survival of 8 months

• gastric tumors resemble diffuse-type gastric adenocarcinomas, are E-cadherin-negative, and are invasive into the muscle layers and regional lymph nodes

• intramucosal adenocarcinomas with signet ring cell feature is seen in 2 of 4 mice at 6 months of age

• gastric premalignant lesions such as atrophic gastritis, metaplasia or dysplasia are not seen at 4 and 5 months of age

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
stomach cancer		DOID:10534	OMIM:613659	J:212549

Allelic Composition	Cdh1^tm2Kem/Cdh1^tm2Kem Smad4^tm2.1Cxd/Smad4^tm2.1Cxd Trp53^tm1Brn/Trp53^tm1Brn Tg(Pdx1-cre)6Tuv/0
Genetic Background	involves: 129 * C57BL/6 * FVB/N

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Cdh1^tm2Kem mutation (1 available); any Cdh1 mutation (171 available)
Smad4^tm2.1Cxd mutation (2 available); any Smad4 mutation (43 available)
Tg(Pdx1-cre)6Tuv mutation (3 available)
Trp53^tm1Brn mutation (18 available); any Trp53 mutation (232 available)

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

neoplasm

increased gastric adenocarcinoma incidence ( J:212549 )

• mice develop gastric adenocarcinomas with a median tumor-free survival of 9.4 months but do not develop distant metastases

digestive/alimentary system

increased gastric adenocarcinoma incidence ( J:212549 )

• mice develop gastric adenocarcinomas with a median tumor-free survival of 9.4 months but do not develop distant metastases

Allelic Composition	Cdh1^tm2Kem/Cdh1⁺ Smad4^tm2.1Cxd/Smad4^tm2.1Cxd Trp53^tm1Brn/Trp53^tm1Brn Tg(MMTV-cre)7Mul/0
Genetic Background	involves: 129 * C57BL/6 * FVB/N

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Cdh1^tm2Kem mutation (1 available); any Cdh1 mutation (171 available)
Smad4^tm2.1Cxd mutation (2 available); any Smad4 mutation (43 available)
Tg(MMTV-cre)7Mul mutation (0 available)
Trp53^tm1Brn mutation (18 available); any Trp53 mutation (232 available)

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

neoplasm

increased mammary adenocarcinoma incidence ( J:212549 )

• mice develop mammary gland carcinoma with a median tumor-free survival of 10.4 months of age

• tumors are invasive ductal carcinomas with a squamous component, however lobular carcinomas are not seen

increased metastatic potential ( J:212549 )

• 33% of mice show lung metastasis

integument

increased mammary adenocarcinoma incidence ( J:212549 )

• mice develop mammary gland carcinoma with a median tumor-free survival of 10.4 months of age

• tumors are invasive ductal carcinomas with a squamous component, however lobular carcinomas are not seen

endocrine/exocrine glands

increased mammary adenocarcinoma incidence ( J:212549 )

• mice develop mammary gland carcinoma with a median tumor-free survival of 10.4 months of age

• tumors are invasive ductal carcinomas with a squamous component, however lobular carcinomas are not seen

Allelic Composition	Pten^tm2Mak/Pten^tm2Mak Smad4^tm2.1Cxd/Smad4^tm2.1Cxd Tg(KRT5-cre)1Xya/0
Genetic Background	involves: 129P2/OlaHsd * 129S6/SvEvTac

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Pten^tm2Mak mutation (4 available); any Pten mutation (81 available)
Smad4^tm2.1Cxd mutation (2 available); any Smad4 mutation (43 available)
Tg(KRT5-cre)1Xya mutation (0 available)

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

digestive/alimentary system

increased stomach tumor incidence ( J:101602 )

• some die of stomach carcinomas by 3 months of age

mortality/aging

premature death ( J:101602 )

• some die by 3 months of age due to stomach carcinomas

neoplasm

increased stomach tumor incidence ( J:101602 )

• some die of stomach carcinomas by 3 months of age

increased skin tumor incidence ( J:101602 )

• tumor formation is accelerated in comparison to conditional keratinocyte targeted Smad4^tm2.1Cxd or Pten^tm2Mak mutant mice

increased skin papilloma incidence ( J:101602 )

• develop visible squamous papillomas on their backs at 2 months of age

increased carcinoma incidence ( J:101602 )

• some die of stomach carcinomas by 3 months of age

decreased tumor latency ( J:101602 )

• tumor formation is accelerated in comparison to conditional keratinocyte targeted Smad4^tm2.1Cxd or Pten^tm2Mak mutant mice

integument

increased keratinocyte proliferation ( J:101602 )

• exhibit persistently proliferating follicular keratinocytes

epithelioid cyst ( J:101602 )

• exhibit enlarged cysts surrounded by a multilayered epithelium filled with keratinized debris or pigments

alopecia ( J:101602 )

• exhibit obvious hair loss 2 months after birth, about 1 month earlier than conditional keratinocyte targeted Smad4^tm2.1Cxd mutant mice

thick hair follicle outer root sheath ( J:101602 )

• outer root sheath is thicker at P18

abnormal hair follicle regression ( J:101602 )

• hair follicles fail to go into catagen stage, indicating blocked regression

increased hair follicle cell proliferation ( J:101602 )

• hair follicles have significantly more proliferating cells at P18 than conditional keratinocyte targeted Pten^tm2Mak mutant mice

thick epidermis ( J:101602 )

• thickened epidermis is observed at P18

increased skin tumor incidence ( J:101602 )

• tumor formation is accelerated in comparison to conditional keratinocyte targeted Smad4^tm2.1Cxd or Pten^tm2Mak mutant mice

increased skin papilloma incidence ( J:101602 )

• develop visible squamous papillomas on their backs at 2 months of age

cellular

increased keratinocyte proliferation ( J:101602 )

• exhibit persistently proliferating follicular keratinocytes

growth/size/body

epithelioid cyst ( J:101602 )

• exhibit enlarged cysts surrounded by a multilayered epithelium filled with keratinized debris or pigments

Allelic Composition	Smad4^tm2.1Cxd/Smad4^tm2.1Cxd Trp53^tm1Brn/Trp53^tm1Brn Tg(Vil1-cre)20Syr/0
Genetic Background	involves: 129P2/OlaHsd * 129S6/SvEvTac * C57BL/6 * DBA/2

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Smad4^tm2.1Cxd mutation (2 available); any Smad4 mutation (43 available)
Tg(Vil1-cre)20Syr mutation (3 available)
Trp53^tm1Brn mutation (18 available); any Trp53 mutation (232 available)

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

neoplasm

increased intestinal adenocarcinoma incidence ( J:212549 )

• mice develop intestinal adenocarcinomas with a median tumor-free survival of 5.4 months of age and no distant metastases are seen

digestive/alimentary system

increased intestinal adenocarcinoma incidence ( J:212549 )

• mice develop intestinal adenocarcinomas with a median tumor-free survival of 5.4 months of age and no distant metastases are seen

Allelic Composition	Smad4^tm2.1Cxd/Smad4^tm2.1Cxd Trp53^tm1Brn/Trp53^tm1Brn Tg(Pdx1-cre)6Tuv/0
Genetic Background	involves: 129P2/OlaHsd * 129S6/SvEvTac * C57BL/6 * FVB/N

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Smad4^tm2.1Cxd mutation (2 available); any Smad4 mutation (43 available)
Tg(Pdx1-cre)6Tuv mutation (3 available)
Trp53^tm1Brn mutation (18 available); any Trp53 mutation (232 available)

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

neoplasm

neoplasm ( J:212549 )

N	• in general, mice do not develop gastric adenocarcinomas, with only one mouse seen to develop it

Allelic Composition	Smad4^tm2.1Cxd/Smad4^tm2.1Cxd Trp53^tm1Brn/Trp53^tm1Brn Tg(MMTV-cre)7Mul/0
Genetic Background	involves: 129P2/OlaHsd * 129S6/SvEvTac * FVB/N

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Smad4^tm2.1Cxd mutation (2 available); any Smad4 mutation (43 available)
Tg(MMTV-cre)7Mul mutation (0 available)
Trp53^tm1Brn mutation (18 available); any Trp53 mutation (232 available)

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

neoplasm

increased mammary adenocarcinoma incidence ( J:212549 )

• mice develop mammary gland carcinoma with a median tumor-free survival of 12.1 months of age

increased metastatic potential ( J:212549 )

• 35.7% of mice show lung metastasis

endocrine/exocrine glands

increased mammary adenocarcinoma incidence ( J:212549 )

• mice develop mammary gland carcinoma with a median tumor-free survival of 12.1 months of age

integument

increased mammary adenocarcinoma incidence ( J:212549 )

• mice develop mammary gland carcinoma with a median tumor-free survival of 12.1 months of age

Allelic Composition	Smad4^tm2.1Cxd/Smad4^tm2.1Cxd Kdr^tm1(cre)Sato/Kdr⁺
Genetic Background	involves: 129S1/Sv * 129S6/SvEvTac

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Kdr^tm1(cre)Sato mutation (1 available); any Kdr mutation (71 available)
Smad4^tm2.1Cxd mutation (2 available); any Smad4 mutation (43 available)

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

mortality/aging

embryonic lethality during organogenesis, complete penetrance ( J:112269 )

• die between E9.5 and E10.5

embryo

abnormal vitelline vasculature morphology ( J:112269 )

• all exhibit angiogenesis defects as only the primary vascular plexus is observed in E9.5 and E10.5 yolk sacs

abnormal embryonic hematopoiesis ( J:112269 )

• the number of hematopoietic colonies in a hematopoietic progenitor assay at E8.5 is decreased by about 50%

cardiovascular system

abnormal vitelline vasculature morphology ( J:112269 )

• all exhibit angiogenesis defects as only the primary vascular plexus is observed in E9.5 and E10.5 yolk sacs

abnormal trabecula carnea morphology ( J:112269 )

• trabeculae in the ventricles is much thinner at E9.5

absent atrioventricular cushions ( J:112269 )

• the atrioventricular canal endocardial cushion is absent

hematopoietic system

abnormal embryonic hematopoiesis ( J:112269 )

• the number of hematopoietic colonies in a hematopoietic progenitor assay at E8.5 is decreased by about 50%

muscle

abnormal trabecula carnea morphology ( J:112269 )

• trabeculae in the ventricles is much thinner at E9.5

Allelic Composition	Kras^tm4Tyj/Kras⁺ Smad4^tm2.1Cxd/Smad4^tm2.1Cxd Tg(Krt1-15-cre/PGR*)22Cot/0
Genetic Background	involves: 129S4/SvJae * 129S6/SvEvTac * C57BL/6 * C57BL/6J * SJL/J

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Kras^tm4Tyj mutation (9 available); any Kras mutation (76 available)
Smad4^tm2.1Cxd mutation (2 available); any Smad4 mutation (43 available)
Tg(Krt1-15-cre/PGR*)22Cot mutation (2 available)

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

neoplasm

increased skin tumor incidence ( J:203922 )

• mice rapidly develop skin tumors beginning 1 month after induction with topical application of RU486 to the back of the skin with 100% penetrance

increased skin squamous cell carcinoma incidence ( J:203922 )

• tumors that develop after RU486 induction are well-to-moderately differentiated squamous cell carcinomas with an epidermal lineage or basaloid squamous cell carcinomas of unknown stem cell origin

increased trichoepithelioma incidence ( J:203922 )

• a subset of benign or locally invasive tumors form adjacent to the squamous cell carcinoma precursor lesions, which are of hair follicle (trichoepitheliomas, basaloid squamous cell carcinoma) or sebaceous gland origin (sebaceous adenomas) after induction with topical application of RU486

increased metastatic potential ( J:203922 )

• metastases develop between 8 and 18 weeks after induction with RU486, with 28% of tumor-bearing mice developing lung metastasis and 1 of 18 mice showing lymph node metastasis

increased adenoma incidence ( J:203922 )

increased papilloma incidence ( J:203922 )

• a few benign papillomas are seen after induction with topical application of RU486

integument

increased skin tumor incidence ( J:203922 )

• mice rapidly develop skin tumors beginning 1 month after induction with topical application of RU486 to the back of the skin with 100% penetrance

increased skin squamous cell carcinoma incidence ( J:203922 )

• tumors that develop after RU486 induction are well-to-moderately differentiated squamous cell carcinomas with an epidermal lineage or basaloid squamous cell carcinomas of unknown stem cell origin

increased trichoepithelioma incidence ( J:203922 )

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
squamous cell carcinoma		DOID:1749		J:203922

Allelic Composition	Pten^tm1Hwu/Pten^tm1Hwu Smad4^tm2.1Cxd/Smad4^tm2.1Cxd Tg(Alb1-cre)1Dlr/0
Genetic Background	involves: 129S4/SvJae * 129S6/SvEvTac * FVB/N

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Pten^tm1Hwu mutation (16 available); any Pten mutation (81 available)
Smad4^tm2.1Cxd mutation (2 available); any Smad4 mutation (43 available)
Tg(Alb1-cre)1Dlr mutation (3 available)

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

mortality/aging

premature death ( J:111718 )

• all mutants die before 10 months of age

endocrine/exocrine glands

abnormal bile duct morphology ( J:111718 )

• increase in branching of bile ducts in the liver

liver/biliary system

abnormal bile duct morphology ( J:111718 )

• increase in branching of bile ducts in the liver

enlarged liver ( J:111718 )

• increase in liver size and weight due to fat accumulation in the liver

increased liver weight ( J:111718 )

hepatic steatosis ( J:111718 )

increased cholangiocarcinoma incidence ( J:111718 )

• at 2 months of age, hyperplastic foci emerge from bile ducts and continue to grow, leading to tumor formation in all mice at 4-7 months of age; tumors are intrahepatic cholangiocellular carcinoma

neoplasm

increased cholangiocarcinoma incidence ( J:111718 )

• at 2 months of age, hyperplastic foci emerge from bile ducts and continue to grow, leading to tumor formation in all mice at 4-7 months of age; tumors are intrahepatic cholangiocellular carcinoma

growth/size/body

enlarged liver ( J:111718 )

• increase in liver size and weight due to fat accumulation in the liver

increased liver weight ( J:111718 )

Allelic Composition	Smad4^tm2.1Cxd/Smad4^tm2.1Cxd Tg(KRT5-cre)1Xya/0
Genetic Background	involves: 129S6/SvEvTac

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Smad4^tm2.1Cxd mutation (2 available); any Smad4 mutation (43 available)
Tg(KRT5-cre)1Xya mutation (0 available)

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

mortality/aging

premature death ( J:101602 )

• do not survive more than 15 months

neoplasm

increased skin tumor incidence ( J:101602 )

• start to develop skin tumors around 5 months of age and by 12 months of age, 70% exhibit visible tumors

increased skin papilloma incidence ( J:101602 )

• most are well-differentiated squamous cell carcinomas and squamous papillomas

increased carcinoma incidence ( J:101602 )

• most are well-differentiated squamous cell carcinomas and squamous papillomas

integument

alopecia ( J:101602 )

• exhibit progressive hair loss that is first evident at P20, is obvious at 3 months of age, and generalized alopecia is seen by 7 months of age

abnormal hypodermis morphology ( J:101602 )

• cysts are seen in the hypodermis

abnormal hair follicle morphology ( J:101602 )

• increase in cell proliferation in hair follicle compared to controls at P25

• hair follicles are disordered and hypertrophied

thick hair follicle outer root sheath ( J:101602 )

• the outer root sheath is abnormally thick and exhibits an increase in cell proliferation in the first anagen at P15

enlarged hair follicles ( J:101602 )

• size of hair follicles is increased at 2 months of age

abnormal hair follicle regression ( J:101602 )

• hair follicles fail to regress and persist in an abnormal anagen phase; by P30 when a new anagen phase starts in controls, homozygotes exhibit thickened and distored follicles

• lower number of apoptotic cells in the hair bulb of early catagen hair follicles

thick epidermis stratum basale ( J:101602 )

• basal layer of the epidermis is thickened

hyperkeratosis ( J:101602 )

• severe hyperkeratosis in the esophagus at 7 months of age

abnormal keratinocyte morphology ( J:101602 )

• number of keratinocytes is increased in the epidermis and hair follicles

thick epidermis ( J:101602 )

• increase in epidermal proliferation

abnormal skin appearance ( J:101602 )

• black and white cysts are seen through out the skin surface

thick skin ( J:101602 )

• skin is thick and stiff

increased skin tumor incidence ( J:101602 )

• start to develop skin tumors around 5 months of age and by 12 months of age, 70% exhibit visible tumors

increased skin papilloma incidence ( J:101602 )

• most are well-differentiated squamous cell carcinomas and squamous papillomas

abnormal keratinocyte physiology ( J:101602 )

• response of keratinocytes to growth inhibition by TGF-beta1 is impaired

increased keratinocyte proliferation ( J:101602 )

• increase in keratinocyte proliferation

cellular

increased keratinocyte proliferation ( J:101602 )

• increase in keratinocyte proliferation

Allelic Composition	Smad4^tm2.1Cxd/Smad4^tm2.1Cxd Tg(Pou5f1-cre/ERT2)#Ysa/0
Genetic Background	involves: 129S6/SvEvTac

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Smad4^tm2.1Cxd mutation (2 available); any Smad4 mutation (43 available)
Tg(Pou5f1-cre/ERT2)#Ysa mutation (0 available)

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

reproductive system

abnormal male meiosis ( J:191052 )

• following tamoxifen treatment at E10.5-E11.5, some male germ cells abnormally enter meiosis at E14.5

Allelic Composition	Smad4^tm2.1Cxd/Smad4^tm2.1Cxd Tg(ACTA1-cre)AMcle/0
Genetic Background	involves: 129S6/SvEvTac * C57BL/6

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Smad4^tm2.1Cxd mutation (2 available); any Smad4 mutation (43 available)
Tg(ACTA1-cre)AMcle mutation (1 available)

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

mortality/aging

embryonic lethality during organogenesis, incomplete penetrance ( J:164492 )

• significant midgestational lethality occurs between E13.5 and E14.5 with only 2 viable mutant fetuses (and 6 dead) out of 34 recovered at E14.5

• 2 viable fetuses (8 dead) are recovered at E18.5 (2 mutant/50 total)

prenatal lethality, complete penetrance ( J:164492 )

• no live mutants are recovered after birth

cardiovascular system

abnormal trabecula carnea morphology ( J:164492 )

• decreased density of trabeculae in ventricles is observed at E13.5

thin ventricle myocardium compact layer ( J:164492 )

• thinning of compact layer of ventricular myocardium is observed at E13.5

double outlet right ventricle ( J:164492 )

• observed at E13.5; defect is more closely related to aortic orifice in mutants

ventricular septal defect ( J:164492 )

• observed at E13.5, resulting from due to deficiency of mesenchyme in the region where outflow tract and AV cushions should meet

abnormal heart right ventricle morphology ( J:164492 )

• in E13.5 mutatnts, only a small fibrous ridge separates the aortic valve from right ventricular outflow tract, as outlet cushions are proximally not fused

abnormal heart ventricle outflow tract morphology ( J:164492 )

• bifurcated outflow tract is in right ventricle, not over ventricular septum

muscle

abnormal trabecula carnea morphology ( J:164492 )

• decreased density of trabeculae in ventricles is observed at E13.5

thin ventricle myocardium compact layer ( J:164492 )

• thinning of compact layer of ventricular myocardium is observed at E13.5

Allelic Composition	Smad4^tm2.1Cxd/Smad4^tm2.1Cxd Tg(Krt1-15-cre/PGR*)22Cot/0
Genetic Background	involves: 129S6/SvEvTac * C57BL/6 * C57BL/6J * SJL/J

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Smad4^tm2.1Cxd mutation (2 available); any Smad4 mutation (43 available)
Tg(Krt1-15-cre/PGR*)22Cot mutation (2 available)

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

endocrine/exocrine glands

enlarged sebaceous gland ( J:203922 )

• following topical application of RU486 to the back of the skin at 3 weeks of age for 5 days

integument

enlarged sebaceous gland ( J:203922 )

• following topical application of RU486 to the back of the skin at 3 weeks of age for 5 days

abnormal hair growth ( J:203922 )

• mice initially develop hair loss following topical application of RU486 to the back of the skin at 3 weeks of age for 5 days

hair follicle degeneration ( J:203922 )

• degenerated hair follicles are seen following topical application of RU486 to the back of the skin at 3 weeks of age for 5 days

neoplasm

neoplasm ( J:203922 )

N	• induction with RU486 does not result in development of spontaneous skin tumors

Allelic Composition	Smad4^tm2.1Cxd/Smad4^tm2.1Cxd Tg(Dppa3-cre/Esr1*)3Sait/0
Genetic Background	involves: 129S6/SvEvTac * C57BL/6 * DBA

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Smad4^tm2.1Cxd mutation (2 available); any Smad4 mutation (43 available)
Tg(Dppa3-cre/Esr1*)3Sait mutation (0 available)

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

reproductive system

abnormal male meiosis ( J:191052 )

• following tamoxifen treatment at E10.5-E11.5, some male germ cells abnormally enter meiosis at E14.5

Allelic Composition	Smad4^tm2.1Cxd/Smad4^tm2.1Cxd Tg(Sp7-tTA,tetO-EGFP/cre)1Amc/0
Genetic Background	involves: 129S6/SvEvTac * C57BL/6J * CD-1

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Smad4^tm2.1Cxd mutation (2 available); any Smad4 mutation (43 available)
Tg(Sp7-tTA,tetO-EGFP/cre)1Amc mutation (2 available)

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

mortality/aging

premature death ( J:211171 )

• almost none of the mutants survive to 8 weeks

• lethality is not alleviated by paste-formula food or by keeping pups with the mother

postnatal lethality, incomplete penetrance ( J:211171 )

• about 50% of pups die by P14 and almost none survive to 8 weeks

skeleton

abnormal osteoblast physiology ( J:211171 )

• osteoblasts do not function properly, depositing abnormal collagen into the skeletal extracellular matrix

abnormal tooth morphology ( J:211171 )

• severe dental abnormalities

small incisors ( J:211171 )

• underdeveloped incisors at P28

abnormal enamel morphology ( J:211171 )

• yellow or even black dental discoloration typical of enamel hypoplasia

malocclusion ( J:211171 )

• mice develop oral malocclusion

decreased osteoclast cell number ( J:211171 )

• TRAP-positive osteoclasts are very sparse on the residual trabeculae, endocortical and periosteal surfaces of bones

abnormal tibia morphology ( J:211171 )

• tibia are small but morphologically normal

decreased diameter of tibia ( J:211171 )

• tibias are narrow at the mid-diaphysis with a total cross-sectional tissue area reduced 43% relative to controls

short tibia ( J:211171 )

• at P28, tibias are about 22% shorter relative to controls

clavicle hypoplasia ( J:211171 )

abnormal long bone diaphysis morphology ( J:211171 )

• diaphyseal medullary space is inappropriately populated by an excessive amount of trabecular bone

rib fractures ( J:211171 )

• multiple rib fractures are seen at 8 weeks of age

abnormal bone collagen fibril morphology ( J:211171 )

• marker analysis indicates abnormal thickness or packing density of collagen fibers in tibia and delayed differentiation of osteoblasts

decreased bone mineral density ( J:211171 )

• craniofacial and axial skeleton are severely under mineralized

• bone mineral density in P28 tibias is reduced 20% relative to controls

• hypomineralized interparietal bones

abnormal compact bone lamellar structure ( J:211171 )

• cortical bone is primarily woven rather than lamellar

decreased compact bone thickness ( J:211171 )

• cortical thickness is decreased by 15%

abnormal osteocyte morphology ( J:211171 )

• osteocyte density is increased in the cortex of bones, but no differences in cancellous bone

abnormal trabecular bone morphology ( J:211171 )

• trabecular bone populates the entire diaphysis instead of being restricted to primary and secondary ossification centers

• trabecular structures in the diaphysis of tibiae are bone and not cartilage left behind during resorption of endochondral cartilage template

delayed bone ossification ( J:211171 )

craniofacial

abnormal tooth morphology ( J:211171 )

• severe dental abnormalities

small incisors ( J:211171 )

• underdeveloped incisors at P28

abnormal enamel morphology ( J:211171 )

• yellow or even black dental discoloration typical of enamel hypoplasia

malocclusion ( J:211171 )

• mice develop oral malocclusion

growth/size/body

abnormal tooth morphology ( J:211171 )

• severe dental abnormalities

small incisors ( J:211171 )

• underdeveloped incisors at P28

abnormal enamel morphology ( J:211171 )

• yellow or even black dental discoloration typical of enamel hypoplasia

malocclusion ( J:211171 )

• mice develop oral malocclusion

small thoracic cavity ( J:211171 )

decreased body size ( J:211171 )

• pups are slightly smaller at birth and mice are severely runted by P28

hematopoietic system

decreased osteoclast cell number ( J:211171 )

• TRAP-positive osteoclasts are very sparse on the residual trabeculae, endocortical and periosteal surfaces of bones

immune system

decreased osteoclast cell number ( J:211171 )

• TRAP-positive osteoclasts are very sparse on the residual trabeculae, endocortical and periosteal surfaces of bones

limbs/digits/tail

abnormal tibia morphology ( J:211171 )

• tibia are small but morphologically normal

decreased diameter of tibia ( J:211171 )

• tibias are narrow at the mid-diaphysis with a total cross-sectional tissue area reduced 43% relative to controls

short tibia ( J:211171 )

• at P28, tibias are about 22% shorter relative to controls

cellular

abnormal osteoblast physiology ( J:211171 )

• osteoblasts do not function properly, depositing abnormal collagen into the skeletal extracellular matrix

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
osteogenesis imperfecta		DOID:12347	OMIM:PS166200	J:211171

Allelic Composition	Smad4^tm2.1Cxd/Smad4⁺ Tg(Sp7-tTA,tetO-EGFP/cre)1Amc/0
Genetic Background	involves: 129S6/SvEvTac * C57BL/6J * CD-1

Find Mice

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

craniofacial

malocclusion ( J:211171 )

• mice develop oral malocclusion

skeleton

malocclusion ( J:211171 )

• mice develop oral malocclusion

increased compact bone thickness ( J:211171 )

• cortical thickness is 23% higher

growth/size/body

malocclusion ( J:211171 )

• mice develop oral malocclusion

Allelic Composition	Smad4^tm2.1Cxd/Smad4^tm2.1Cxd Tg(Capn8-cre)1Xya/0
Genetic Background	involves: 129S6/SvEvTac * FVB/N

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Smad4^tm2.1Cxd mutation (2 available); any Smad4 mutation (43 available)
Tg(Capn8-cre)1Xya mutation (0 available)

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

digestive/alimentary system

digestive/alimentary phenotype ( J:153563 )

N	• no significant differences in gastric epithelium relative to wild-type are observed at 1 month postnatal

Allelic Composition	Smad4^tm2.1Cxd/Smad4^tm2.1Cxd Tg(Nes-cre)1Atp/0
Genetic Background	involves: 129S6/SvEvTac * FVB/N

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Smad4^tm2.1Cxd mutation (2 available); any Smad4 mutation (43 available)
Tg(Nes-cre)1Atp mutation (0 available)

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

mortality/aging

embryonic lethality, complete penetrance ( J:86155 )

• when the Nes-Cre transgene is paternally derived, mutant embryos die at early post-implantation stages, however if the Nes-Cre transgene is maternally derived, mutants survive to adulthood

nervous system

decreased Purkinje cell number ( J:86155 )

• number of parvalbumin-containing Purkinje cells is only 43% of that in controls, however hippocampus and synaptic plasticity are normal

abnormal cerebellar molecular layer ( J:86155 )

• number of parvalbumin-positive interneurons in the molecular layer is decreased by 34.4%

behavior/neurological

increased vertical activity ( J:86155 )

• exhibit substantially higher vertical activity, however no differences in the balance bar task, rotarod assay, or horizontal activity

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