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Phenotypes associated with this allele
Allele Symbol
Allele Name
Allele ID
Smad4tm2.1Cxd
targeted mutation 2.1, Chu-Xia Deng
MGI:2386393
Summary 21 genotypes
Jump to Allelic Composition Genetic Background Genotype ID
cn1
Smad4tm2.1Cxd/Smad4tm2.1Cxd
Tg(Foxn1-cre)8Ghr/0
B6.Cg-Smad4tm2.1Cxd Tg(Foxn1-cre)8Ghr MGI:3810117
cn2
Cdh1tm2Kem/Cdh1+
Smad4tm2.1Cxd/Smad4tm2.1Cxd
Trp53tm1Brn/Trp53tm1Brn
Tg(Vil1-cre)20Syr/0
involves: 129 * C57BL/6 * DBA/2 MGI:5634401
cn3
Cdh1tm2Kem/Cdh1+
Smad4tm2.1Cxd/Smad4tm2.1Cxd
Trp53tm1Brn/Trp53tm1Brn
Tg(Pdx1-cre)6Tuv/0
involves: 129 * C57BL/6 * FVB/N MGI:5634400
cn4
Cdh1tm2Kem/Cdh1tm2Kem
Smad4tm2.1Cxd/Smad4tm2.1Cxd
Trp53tm1Brn/Trp53tm1Brn
Tg(Pdx1-cre)6Tuv/0
involves: 129 * C57BL/6 * FVB/N MGI:5634407
cn5
Cdh1tm2Kem/Cdh1+
Smad4tm2.1Cxd/Smad4tm2.1Cxd
Trp53tm1Brn/Trp53tm1Brn
Tg(MMTV-cre)7Mul/0
involves: 129 * C57BL/6 * FVB/N MGI:5634403
cn6
Ptentm2Mak/Ptentm2Mak
Smad4tm2.1Cxd/Smad4tm2.1Cxd
Tg(KRT5-cre)1Xya/0
involves: 129P2/OlaHsd * 129S6/SvEvTac MGI:3607778
cn7
Smad4tm2.1Cxd/Smad4tm2.1Cxd
Trp53tm1Brn/Trp53tm1Brn
Tg(Vil1-cre)20Syr/0
involves: 129P2/OlaHsd * 129S6/SvEvTac * C57BL/6 * DBA/2 MGI:5634402
cn8
Smad4tm2.1Cxd/Smad4tm2.1Cxd
Trp53tm1Brn/Trp53tm1Brn
Tg(Pdx1-cre)6Tuv/0
involves: 129P2/OlaHsd * 129S6/SvEvTac * C57BL/6 * FVB/N MGI:5634408
cn9
Smad4tm2.1Cxd/Smad4tm2.1Cxd
Trp53tm1Brn/Trp53tm1Brn
Tg(MMTV-cre)7Mul/0
involves: 129P2/OlaHsd * 129S6/SvEvTac * FVB/N MGI:5634404
cn10
Smad4tm2.1Cxd/Smad4tm2.1Cxd
Kdrtm1(cre)Sato/Kdr+
involves: 129S1/Sv * 129S6/SvEvTac MGI:3687383
cn11
Krastm4Tyj/Kras+
Smad4tm2.1Cxd/Smad4tm2.1Cxd
Tg(Krt1-15-cre/PGR)22Cot/0
involves: 129S4/SvJae * 129S6/SvEvTac * C57BL/6 * C57BL/6J * SJL/J MGI:5556259
cn12
Ptentm1Hwu/Ptentm1Hwu
Smad4tm2.1Cxd/Smad4tm2.1Cxd
Tg(Alb1-cre)1Dlr/0
involves: 129S4/SvJae * 129S6/SvEvTac * FVB/N MGI:4839217
cn13
Smad4tm2.1Cxd/Smad4tm2.1Cxd
Tg(KRT5-cre)1Xya/0
involves: 129S6/SvEvTac MGI:3607725
cn14
Smad4tm2.1Cxd/Smad4tm2.1Cxd
Tg(Pou5f1-cre/ERT2)#Ysa/0
involves: 129S6/SvEvTac MGI:5615472
cn15
Smad4tm2.1Cxd/Smad4tm2.1Cxd
Tg(ACTA1-cre)AMcle/0
involves: 129S6/SvEvTac * C57BL/6 MGI:5297811
cn16
Smad4tm2.1Cxd/Smad4tm2.1Cxd
Tg(Krt1-15-cre/PGR)22Cot/0
involves: 129S6/SvEvTac * C57BL/6 * C57BL/6J * SJL/J MGI:5556247
cn17
Smad4tm2.1Cxd/Smad4tm2.1Cxd
Tg(Dppa3-cre/Esr1*)3Sait/0
involves: 129S6/SvEvTac * C57BL/6 * DBA MGI:5462061
cn18
Smad4tm2.1Cxd/Smad4+
Tg(Sp7-tTA,tetO-EGFP/cre)1Amc/0
involves: 129S6/SvEvTac * C57BL/6J * CD-1 MGI:5604140
cn19
Smad4tm2.1Cxd/Smad4tm2.1Cxd
Tg(Sp7-tTA,tetO-EGFP/cre)1Amc/0
involves: 129S6/SvEvTac * C57BL/6J * CD-1 MGI:5604139
cn20
Smad4tm2.1Cxd/Smad4tm2.1Cxd
Tg(Capn8-cre)1Xya/0
involves: 129S6/SvEvTac * FVB/N MGI:4365917
cn21
Smad4tm2.1Cxd/Smad4tm2.1Cxd
Tg(Nes-cre)1Atp/0
involves: 129S6/SvEvTac * FVB/N MGI:3608993


Genotype
MGI:3810117
cn1
Allelic
Composition
Smad4tm2.1Cxd/Smad4tm2.1Cxd
Tg(Foxn1-cre)8Ghr/0
Genetic
Background
B6.Cg-Smad4tm2.1Cxd Tg(Foxn1-cre)8Ghr
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Smad4tm2.1Cxd mutation (1 available); any Smad4 mutation (13 available)
Tg(Foxn1-cre)8Ghr mutation (0 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
immune system
• mice exhibit small thymus
• however, the cellularity and histology of the thymus are normal
• unlike in wild type mice, the thymus is resistant to increased cellularity induced by KGF

hematopoietic system
• mice exhibit small thymus
• however, the cellularity and histology of the thymus are normal
• unlike in wild type mice, the thymus is resistant to increased cellularity induced by KGF

endocrine/exocrine glands
• mice exhibit small thymus
• however, the cellularity and histology of the thymus are normal
• unlike in wild type mice, the thymus is resistant to increased cellularity induced by KGF




Genotype
MGI:5634401
cn2
Allelic
Composition
Cdh1tm2Kem/Cdh1+
Smad4tm2.1Cxd/Smad4tm2.1Cxd
Trp53tm1Brn/Trp53tm1Brn
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:
Cdh1tm2Kem mutation (1 available); any Cdh1 mutation (119 available)
Smad4tm2.1Cxd mutation (1 available); any Smad4 mutation (13 available)
Tg(Vil1-cre)20Syr mutation (2 available)
Trp53tm1Brn mutation (13 available); any Trp53 mutation (150 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
digestive/alimentary system
• mice develop intestinal adenocarcinomas with a median tumor-free survival of 5.2 months of age and no distant metastases are seen

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




Genotype
MGI:5634400
cn3
Allelic
Composition
Cdh1tm2Kem/Cdh1+
Smad4tm2.1Cxd/Smad4tm2.1Cxd
Trp53tm1Brn/Trp53tm1Brn
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:
Cdh1tm2Kem mutation (1 available); any Cdh1 mutation (119 available)
Smad4tm2.1Cxd mutation (1 available); any Smad4 mutation (13 available)
Tg(Pdx1-cre)6Tuv mutation (2 available)
Trp53tm1Brn mutation (13 available); any Trp53 mutation (150 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
digestive/alimentary system
• 36% of mice develop duodenal adenocarcinomas
• 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

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

neoplasm
• 36% of mice develop duodenal adenocarcinomas
• 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
• 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
• 24% of mice develop forestomach squamous cell carcinomas

Mouse Models of Human Disease
DO ID OMIM ID(s) Ref(s)
stomach cancer DOID:10534 OMIM:137215
OMIM:613659
J:212549




Genotype
MGI:5634407
cn4
Allelic
Composition
Cdh1tm2Kem/Cdh1tm2Kem
Smad4tm2.1Cxd/Smad4tm2.1Cxd
Trp53tm1Brn/Trp53tm1Brn
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:
Cdh1tm2Kem mutation (1 available); any Cdh1 mutation (119 available)
Smad4tm2.1Cxd mutation (1 available); any Smad4 mutation (13 available)
Tg(Pdx1-cre)6Tuv mutation (2 available)
Trp53tm1Brn mutation (13 available); any Trp53 mutation (150 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
digestive/alimentary system
• mice develop gastric adenocarcinomas with a median tumor-free survival of 9.4 months but do not develop distant metastases

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




Genotype
MGI:5634403
cn5
Allelic
Composition
Cdh1tm2Kem/Cdh1+
Smad4tm2.1Cxd/Smad4tm2.1Cxd
Trp53tm1Brn/Trp53tm1Brn
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:
Cdh1tm2Kem mutation (1 available); any Cdh1 mutation (119 available)
Smad4tm2.1Cxd mutation (1 available); any Smad4 mutation (13 available)
Tg(MMTV-cre)7Mul mutation (0 available)
Trp53tm1Brn mutation (13 available); any Trp53 mutation (150 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
integument
• 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
• 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

neoplasm
• 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
• 33% of mice show lung metastasis




Genotype
MGI:3607778
cn6
Allelic
Composition
Ptentm2Mak/Ptentm2Mak
Smad4tm2.1Cxd/Smad4tm2.1Cxd
Tg(KRT5-cre)1Xya/0
Genetic
Background
involves: 129P2/OlaHsd * 129S6/SvEvTac
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Ptentm2Mak mutation (4 available); any Pten mutation (39 available)
Smad4tm2.1Cxd mutation (1 available); any Smad4 mutation (13 available)
Tg(KRT5-cre)1Xya mutation (0 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
digestive/alimentary system
• some die of stomach carcinomas by 3 months of age

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

neoplasm
• some die of stomach carcinomas by 3 months of age
• tumor formation is accelerated in comparison to conditional keratinocyte targeted Smad4tm2.1Cxd or Ptentm2Mak mutant mice
• develop visible squamous papillomas on their backs at 2 months of age
• some die of stomach carcinomas by 3 months of age
• tumor formation is accelerated in comparison to conditional keratinocyte targeted Smad4tm2.1Cxd or Ptentm2Mak mutant mice

integument
• exhibit persistently proliferating follicular keratinocytes
• exhibit obvious hair loss 2 months after birth, about 1 month earlier than conditional keratinocyte targeted Smad4tm2.1Cxd mutant mice
• outer root sheath is thicker at P18
• hair follicles fail to go into catagen stage, indicating blocked regression
• hair follicles have significantly more proliferating cells at P18 than conditional keratinocyte targeted Ptentm2Mak mutant mice
• thickened epidermis is observed at P18
• exhibit enlarged cysts surrounded by a multilayered epithelium filled with keratinized debris or pigments
• tumor formation is accelerated in comparison to conditional keratinocyte targeted Smad4tm2.1Cxd or Ptentm2Mak mutant mice
• develop visible squamous papillomas on their backs at 2 months of age

cellular
• exhibit persistently proliferating follicular keratinocytes




Genotype
MGI:5634402
cn7
Allelic
Composition
Smad4tm2.1Cxd/Smad4tm2.1Cxd
Trp53tm1Brn/Trp53tm1Brn
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:
Smad4tm2.1Cxd mutation (1 available); any Smad4 mutation (13 available)
Tg(Vil1-cre)20Syr mutation (2 available)
Trp53tm1Brn mutation (13 available); any Trp53 mutation (150 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
digestive/alimentary system
• mice develop intestinal adenocarcinomas with a median tumor-free survival of 5.4 months of age and no distant metastases are seen

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




Genotype
MGI:5634408
cn8
Allelic
Composition
Smad4tm2.1Cxd/Smad4tm2.1Cxd
Trp53tm1Brn/Trp53tm1Brn
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:
Smad4tm2.1Cxd mutation (1 available); any Smad4 mutation (13 available)
Tg(Pdx1-cre)6Tuv mutation (2 available)
Trp53tm1Brn mutation (13 available); any Trp53 mutation (150 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
neoplasm
N
• in general, mice do not develop gastric adenocarcinomas, with only one mouse seen to develop it




Genotype
MGI:5634404
cn9
Allelic
Composition
Smad4tm2.1Cxd/Smad4tm2.1Cxd
Trp53tm1Brn/Trp53tm1Brn
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:
Smad4tm2.1Cxd mutation (1 available); any Smad4 mutation (13 available)
Tg(MMTV-cre)7Mul mutation (0 available)
Trp53tm1Brn mutation (13 available); any Trp53 mutation (150 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
integument
• mice develop mammary gland carcinoma with a median tumor-free survival of 12.1 months of age

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

neoplasm
• mice develop mammary gland carcinoma with a median tumor-free survival of 12.1 months of age
• 35.7% of mice show lung metastasis




Genotype
MGI:3687383
cn10
Allelic
Composition
Smad4tm2.1Cxd/Smad4tm2.1Cxd
Kdrtm1(cre)Sato/Kdr+
Genetic
Background
involves: 129S1/Sv * 129S6/SvEvTac
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Kdrtm1(cre)Sato mutation (1 available); any Kdr mutation (10 available)
Smad4tm2.1Cxd mutation (1 available); any Smad4 mutation (13 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
mortality/aging

embryo
• all exhibit angiogenesis defects as only the primary vascular plexus is observed in E9.5 and E10.5 yolk sacs
• the number of hematopoietic colonies in a hematopoietic progenitor assay at E8.5 is decreased by about 50%

cardiovascular system
• all exhibit angiogenesis defects as only the primary vascular plexus is observed in E9.5 and E10.5 yolk sacs
• trabeculae in the ventricles is much thinner at E9.5
• the atrioventricular canal endocardial cushion is absent

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

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




Genotype
MGI:5556259
cn11
Allelic
Composition
Krastm4Tyj/Kras+
Smad4tm2.1Cxd/Smad4tm2.1Cxd
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:
Krastm4Tyj mutation (6 available); any Kras mutation (35 available)
Smad4tm2.1Cxd mutation (1 available); any Smad4 mutation (13 available)
Tg(Krt1-15-cre/PGR)22Cot mutation (2 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
neoplasm
• mice rapidly develop skin tumors beginning 1 month after induction with topical application of RU486 to the back of the skin with 100% penetrance
• 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
• 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
• 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
• 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
• a few benign papillomas are seen after induction with topical application of RU486

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

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




Genotype
MGI:4839217
cn12
Allelic
Composition
Ptentm1Hwu/Ptentm1Hwu
Smad4tm2.1Cxd/Smad4tm2.1Cxd
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:
Ptentm1Hwu mutation (3 available); any Pten mutation (39 available)
Smad4tm2.1Cxd mutation (1 available); any Smad4 mutation (13 available)
Tg(Alb1-cre)1Dlr mutation (2 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
mortality/aging
• all mutants die before 10 months of age

endocrine/exocrine glands
• increase in branching of bile ducts in the liver

liver/biliary system
• increase in branching of bile ducts in the liver
• increase in liver size and weight due to fat accumulation in the liver
• 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
• 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




Genotype
MGI:3607725
cn13
Allelic
Composition
Smad4tm2.1Cxd/Smad4tm2.1Cxd
Tg(KRT5-cre)1Xya/0
Genetic
Background
involves: 129S6/SvEvTac
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Smad4tm2.1Cxd mutation (1 available); any Smad4 mutation (13 available)
Tg(KRT5-cre)1Xya mutation (0 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
mortality/aging
• do not survive more than 15 months

neoplasm
• start to develop skin tumors around 5 months of age and by 12 months of age, 70% exhibit visible tumors
• most are well-differentiated squamous cell carcinomas and squamous papillomas
• most are well-differentiated squamous cell carcinomas and squamous papillomas

integument
• 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
• cysts are seen in the hypodermis
• increase in cell proliferation in hair follicle compared to controls at P25
• hair follicles are disordered and hypertrophied
• the outer root sheath is abnormally thick and exhibits an increase in cell proliferation in the first anagen at P15
• size of hair follicles is increased at 2 months of age
• 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
• basal layer of the epidermis is thickened
• severe hyperkeratosis in the esophagus at 7 months of age
• number of keratinocytes is increased in the epidermis and hair follicles
• increase in epidermal proliferation
• black and white cysts are seen through out the skin surface
• skin is thick and stiff
• start to develop skin tumors around 5 months of age and by 12 months of age, 70% exhibit visible tumors
• most are well-differentiated squamous cell carcinomas and squamous papillomas
• response of keratinocytes to growth inhibition by TGF-beta1 is impaired
• increase in keratinocyte proliferation

cellular
• increase in keratinocyte proliferation




Genotype
MGI:5615472
cn14
Allelic
Composition
Smad4tm2.1Cxd/Smad4tm2.1Cxd
Tg(Pou5f1-cre/ERT2)#Ysa/0
Genetic
Background
involves: 129S6/SvEvTac
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Smad4tm2.1Cxd mutation (1 available); any Smad4 mutation (13 available)
Tg(Pou5f1-cre/ERT2)#Ysa mutation (0 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
reproductive system
• following tamoxifen treatment at E10.5-E11.5, some male germ cells abnormally enter meiosis at E14.5




Genotype
MGI:5297811
cn15
Allelic
Composition
Smad4tm2.1Cxd/Smad4tm2.1Cxd
Tg(ACTA1-cre)AMcle/0
Genetic
Background
involves: 129S6/SvEvTac * C57BL/6
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Smad4tm2.1Cxd mutation (1 available); any Smad4 mutation (13 available)
Tg(ACTA1-cre)AMcle mutation (1 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
mortality/aging
• 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)
• no live mutants are recovered after birth

cardiovascular system
• decreased density of trabeculae in ventricles is observed at E13.5
• thinning of compact layer of ventricular myocardium is observed at E13.5
• observed at E13.5; defect is more closely related to aortic orifice in mutants
• observed at E13.5, resulting from due to deficiency of mesenchyme in the region where outflow tract and AV cushions should meet
• 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
• bifurcated outflow tract is in right ventricle, not over ventricular septum

muscle
• decreased density of trabeculae in ventricles is observed at E13.5
• thinning of compact layer of ventricular myocardium is observed at E13.5




Genotype
MGI:5556247
cn16
Allelic
Composition
Smad4tm2.1Cxd/Smad4tm2.1Cxd
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:
Smad4tm2.1Cxd mutation (1 available); any Smad4 mutation (13 available)
Tg(Krt1-15-cre/PGR)22Cot mutation (2 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
endocrine/exocrine glands
• following topical application of RU486 to the back of the skin at 3 weeks of age for 5 days

integument
• following topical application of RU486 to the back of the skin at 3 weeks of age for 5 days
• mice initially develop hair loss following topical application of RU486 to the back of the skin at 3 weeks of age for 5 days
• 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
N
• induction with RU486 does not result in development of spontaneous skin tumors




Genotype
MGI:5462061
cn17
Allelic
Composition
Smad4tm2.1Cxd/Smad4tm2.1Cxd
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:
Smad4tm2.1Cxd mutation (1 available); any Smad4 mutation (13 available)
Tg(Dppa3-cre/Esr1*)3Sait mutation (0 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
reproductive system
• following tamoxifen treatment at E10.5-E11.5, some male germ cells abnormally enter meiosis at E14.5




Genotype
MGI:5604140
cn18
Allelic
Composition
Smad4tm2.1Cxd/Smad4+
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:
Smad4tm2.1Cxd mutation (1 available); any Smad4 mutation (13 available)
Tg(Sp7-tTA,tetO-EGFP/cre)1Amc mutation (1 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
growth/size/body
• mice develop oral malocclusion

craniofacial
• mice develop oral malocclusion

skeleton
• mice develop oral malocclusion
• cortical thickness is 23% higher




Genotype
MGI:5604139
cn19
Allelic
Composition
Smad4tm2.1Cxd/Smad4tm2.1Cxd
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:
Smad4tm2.1Cxd mutation (1 available); any Smad4 mutation (13 available)
Tg(Sp7-tTA,tetO-EGFP/cre)1Amc mutation (1 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
cellular
• osteoblasts do not function properly, depositing abnormal collagen into the skeletal extracellular matrix

mortality/aging
• almost none of the mutants survive to 8 weeks
• lethality is not alleviated by paste-formula food or by keeping pups with the mother
• about 50% of pups die by P14 and almost none survive to 8 weeks

skeleton
• osteoblasts do not function properly, depositing abnormal collagen into the skeletal extracellular matrix
• severe dental abnormalities
• underdeveloped incisors at P28
• yellow or even black dental discoloration typical of enamel hypoplasia
• mice develop oral malocclusion
• TRAP-positive osteoclasts are very sparse on the residual trabeculae, endocortical and periosteal surfaces of bones
• tibia are small but morphologically normal
• tibias are narrow at the mid-diaphysis with a total cross-sectional tissue area reduced 43% relative to controls
• at P28, tibias are about 22% shorter relative to controls
• diaphyseal medullary space is inappropriately populated by an excessive amount of trabecular bone
• multiple rib fractures are seen at 8 weeks of age
• marker analysis indicates abnormal thickness or packing density of collagen fibers in tibia and delayed differentiation of osteoblasts
• craniofacial and axial skeleton are severely under mineralized
• bone mineral density in P28 tibias is reduced 20% relative to controls
• hypomineralized interparietal bones
• cortical bone is primarily woven rather than lamellar
• cortical thickness is decreased by 15%
• osteocyte density is increased in the cortex of bones, but no differences in cancellous bone
• 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

craniofacial
• severe dental abnormalities
• underdeveloped incisors at P28
• yellow or even black dental discoloration typical of enamel hypoplasia
• mice develop oral malocclusion

growth/size/body
• severe dental abnormalities
• underdeveloped incisors at P28
• yellow or even black dental discoloration typical of enamel hypoplasia
• mice develop oral malocclusion
• pups are slightly smaller at birth and mice are severely runted by P28

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

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

limbs/digits/tail
• tibia are small but morphologically normal
• tibias are narrow at the mid-diaphysis with a total cross-sectional tissue area reduced 43% relative to controls
• at P28, tibias are about 22% shorter relative to controls

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




Genotype
MGI:4365917
cn20
Allelic
Composition
Smad4tm2.1Cxd/Smad4tm2.1Cxd
Tg(Capn8-cre)1Xya/0
Genetic
Background
involves: 129S6/SvEvTac * FVB/N
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Smad4tm2.1Cxd mutation (1 available); any Smad4 mutation (13 available)
Tg(Capn8-cre)1Xya mutation (0 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
digestive/alimentary system
N
• no significant differences in gastric epithelium relative to wild-type are observed at 1 month postnatal




Genotype
MGI:3608993
cn21
Allelic
Composition
Smad4tm2.1Cxd/Smad4tm2.1Cxd
Tg(Nes-cre)1Atp/0
Genetic
Background
involves: 129S6/SvEvTac * FVB/N
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Smad4tm2.1Cxd mutation (1 available); any Smad4 mutation (13 available)
Tg(Nes-cre)1Atp mutation (0 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
mortality/aging
• 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
• number of parvalbumin-containing Purkinje cells is only 43% of that in controls, however hippocampus and synaptic plasticity are normal
• number of parvalbumin-positive interneurons in the molecular layer is decreased by 34.4%

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





Contributing Projects:
Mouse Genome Database (MGD), Gene Expression Database (GXD), Mouse Models of Human Cancer database (MMHCdb) (formerly Mouse Tumor Biology (MTB), Gene Ontology (GO)
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last database update
07/09/2019
MGI 6.14
The Jackson Laboratory