Analysis Tools|
Allele Symbol Allele Name Allele ID |
Smad4tm2.1Cxd targeted mutation 2.1, Chu-Xia Deng MGI:2386393 |
| Summary |
22 genotypes |
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• bone mesenchymal stem cells (BMSCs) isolated from mice infected with adenovirus bearing cre recombinase show reduced BRCM-induced migration and show lack of lamellipodia-like protrusions when placed on a TGF-beta1 gradient
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• mice exhibit small thymus
• however, the cellularity and histology of the thymus are normal
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• unlike in wild type mice, the thymus is resistant to increased cellularity induced by KGF
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• mice exhibit small thymus
• however, the cellularity and histology of the thymus are normal
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• unlike in wild type mice, the thymus is resistant to increased cellularity induced by KGF
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• mice exhibit small thymus
• however, the cellularity and histology of the thymus are normal
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• unlike in wild type mice, the thymus is resistant to increased cellularity induced by KGF
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• mice develop intestinal adenocarcinomas with a median tumor-free survival of 5.2 months of age and no distant metastases are seen
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• mice develop intestinal adenocarcinomas with a median tumor-free survival of 5.2 months of age and no distant metastases are seen
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• most common cause of death is duodenal obstruction, followed by gastric outlet obstruction
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• 36% of mice develop duodenal adenocarcinomas
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• 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
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• 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
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• 24% of mice develop forestomach squamous cell carcinomas
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• 36% of mice develop duodenal adenocarcinomas
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• 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
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Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| stomach cancer | DOID:10534 |
OMIM:613659 |
J:212549 | |
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• mice develop gastric adenocarcinomas with a median tumor-free survival of 9.4 months but do not develop distant metastases
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• mice develop gastric adenocarcinomas with a median tumor-free survival of 9.4 months but do not develop distant metastases
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• 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
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• 33% of mice show lung metastasis
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• 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
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• 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
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• some die of stomach carcinomas by 3 months of age
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• some die by 3 months of age due to stomach carcinomas
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• some die of stomach carcinomas by 3 months of age
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• tumor formation is accelerated in comparison to conditional keratinocyte targeted Smad4tm2.1Cxd or Ptentm2Mak mutant mice
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• develop visible squamous papillomas on their backs at 2 months of age
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• some die of stomach carcinomas by 3 months of age
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• tumor formation is accelerated in comparison to conditional keratinocyte targeted Smad4tm2.1Cxd or Ptentm2Mak mutant mice
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• exhibit persistently proliferating follicular keratinocytes
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• exhibit enlarged cysts surrounded by a multilayered epithelium filled with keratinized debris or pigments
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• exhibit obvious hair loss 2 months after birth, about 1 month earlier than conditional keratinocyte targeted Smad4tm2.1Cxd mutant mice
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• outer root sheath is thicker at P18
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• hair follicles fail to go into catagen stage, indicating blocked regression
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• hair follicles have significantly more proliferating cells at P18 than conditional keratinocyte targeted Ptentm2Mak mutant mice
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• thickened epidermis is observed at P18
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• tumor formation is accelerated in comparison to conditional keratinocyte targeted Smad4tm2.1Cxd or Ptentm2Mak mutant mice
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• develop visible squamous papillomas on their backs at 2 months of age
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• exhibit persistently proliferating follicular keratinocytes
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• exhibit enlarged cysts surrounded by a multilayered epithelium filled with keratinized debris or pigments
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• mice develop intestinal adenocarcinomas with a median tumor-free survival of 5.4 months of age and no distant metastases are seen
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• mice develop intestinal adenocarcinomas with a median tumor-free survival of 5.4 months of age and no distant metastases are seen
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• mice develop mammary gland carcinoma with a median tumor-free survival of 12.1 months of age
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• 35.7% of mice show lung metastasis
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• mice develop mammary gland carcinoma with a median tumor-free survival of 12.1 months of age
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• mice develop mammary gland carcinoma with a median tumor-free survival of 12.1 months of age
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• die between E9.5 and E10.5
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• all exhibit angiogenesis defects as only the primary vascular plexus is observed in E9.5 and E10.5 yolk sacs
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• the number of hematopoietic colonies in a hematopoietic progenitor assay at E8.5 is decreased by about 50%
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• all exhibit angiogenesis defects as only the primary vascular plexus is observed in E9.5 and E10.5 yolk sacs
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• trabeculae in the ventricles is much thinner at E9.5
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• the atrioventricular canal endocardial cushion is absent
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• the number of hematopoietic colonies in a hematopoietic progenitor assay at E8.5 is decreased by about 50%
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• trabeculae in the ventricles is much thinner at E9.5
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• mice rapidly develop skin tumors beginning 1 month after induction with topical application of RU486 to the back of the skin with 100% penetrance
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• 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
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• 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
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• 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
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• 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
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• a few benign papillomas are seen after induction with topical application of RU486
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• mice rapidly develop skin tumors beginning 1 month after induction with topical application of RU486 to the back of the skin with 100% penetrance
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• 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
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• 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
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Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| squamous cell carcinoma | DOID:1749 | J:203922 | ||
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• all mutants die before 10 months of age
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• increase in branching of bile ducts in the liver
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• 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
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• increase in branching of bile ducts in the liver
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• 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
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• increase in liver size and weight due to fat accumulation in the liver
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• 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
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• increase in liver size and weight due to fat accumulation in the liver
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• following tamoxifen treatment at E10.5-E11.5, some male germ cells abnormally enter meiosis at E14.5
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• following tamoxifen treatment at E10.5-E11.5, some male germ cells abnormally enter meiosis at E14.5
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• do not survive more than 15 months
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• start to develop skin tumors around 5 months of age and by 12 months of age, 70% exhibit visible tumors
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• most are well-differentiated squamous cell carcinomas and squamous papillomas
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• most are well-differentiated squamous cell carcinomas and squamous papillomas
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• 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
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• cysts are seen in the hypodermis
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• increase in cell proliferation in hair follicle compared to controls at P25
• hair follicles are disordered and hypertrophied
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• the outer root sheath is abnormally thick and exhibits an increase in cell proliferation in the first anagen at P15
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• size of hair follicles is increased at 2 months of age
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• 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
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• basal layer of the epidermis is thickened
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• severe hyperkeratosis in the esophagus at 7 months of age
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• number of keratinocytes is increased in the epidermis and hair follicles
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• increase in epidermal proliferation
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• black and white cysts are seen through out the skin surface
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• skin is thick and stiff
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• skin is thick and stiff
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• start to develop skin tumors around 5 months of age and by 12 months of age, 70% exhibit visible tumors
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• most are well-differentiated squamous cell carcinomas and squamous papillomas
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• response of keratinocytes to growth inhibition by TGF-beta1 is impaired
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• increase in keratinocyte proliferation
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• increase in keratinocyte proliferation
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• 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)
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• no live mutants are recovered after birth
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• decreased density of trabeculae in ventricles is observed at E13.5
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• thinning of compact layer of ventricular myocardium is observed at E13.5
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• observed at E13.5; defect is more closely related to aortic orifice in mutants
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• observed at E13.5, resulting from due to deficiency of mesenchyme in the region where outflow tract and AV cushions should meet
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• 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
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• bifurcated outflow tract is in right ventricle, not over ventricular septum
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• decreased density of trabeculae in ventricles is observed at E13.5
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• thinning of compact layer of ventricular myocardium is observed at E13.5
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• following topical application of RU486 to the back of the skin at 3 weeks of age for 5 days
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• following topical application of RU486 to the back of the skin at 3 weeks of age for 5 days
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• mice initially develop hair loss following topical application of RU486 to the back of the skin at 3 weeks of age for 5 days
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• degenerated hair follicles are seen following topical application of RU486 to the back of the skin at 3 weeks of age for 5 days
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| N |
• induction with RU486 does not result in development of spontaneous skin tumors
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• following tamoxifen treatment at E10.5-E11.5, some male germ cells abnormally enter meiosis at E14.5
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• following tamoxifen treatment at E10.5-E11.5, some male germ cells abnormally enter meiosis at E14.5
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• mice develop oral malocclusion
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• mice develop oral malocclusion
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• cortical thickness is 23% higher
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• mice develop oral malocclusion
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• almost none of the mutants survive to 8 weeks
• lethality is not alleviated by paste-formula food or by keeping pups with the mother
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• about 50% of pups die by P14 and almost none survive to 8 weeks
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• osteoblasts do not function properly, depositing abnormal collagen into the skeletal extracellular matrix
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• severe dental abnormalities
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• underdeveloped incisors at P28
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• yellow or even black dental discoloration typical of enamel hypoplasia
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• mice develop oral malocclusion
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• TRAP-positive osteoclasts are very sparse on the residual trabeculae, endocortical and periosteal surfaces of bones
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• tibia are small but morphologically normal
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• tibias are narrow at the mid-diaphysis with a total cross-sectional tissue area reduced 43% relative to controls
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• at P28, tibias are about 22% shorter relative to controls
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• diaphyseal medullary space is inappropriately populated by an excessive amount of trabecular bone
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• multiple rib fractures are seen at 8 weeks of age
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• marker analysis indicates abnormal thickness or packing density of collagen fibers in tibia and delayed differentiation of osteoblasts
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• craniofacial and axial skeleton are severely under mineralized
• bone mineral density in P28 tibias is reduced 20% relative to controls
• hypomineralized interparietal bones
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• cortical bone is primarily woven rather than lamellar
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• cortical thickness is decreased by 15%
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• osteocyte density is increased in the cortex of bones, but no differences in cancellous bone
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• 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
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• severe dental abnormalities
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• underdeveloped incisors at P28
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• yellow or even black dental discoloration typical of enamel hypoplasia
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• mice develop oral malocclusion
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• severe dental abnormalities
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• underdeveloped incisors at P28
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• yellow or even black dental discoloration typical of enamel hypoplasia
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• mice develop oral malocclusion
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• pups are slightly smaller at birth and mice are severely runted by P28
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• TRAP-positive osteoclasts are very sparse on the residual trabeculae, endocortical and periosteal surfaces of bones
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• TRAP-positive osteoclasts are very sparse on the residual trabeculae, endocortical and periosteal surfaces of bones
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• tibia are small but morphologically normal
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• tibias are narrow at the mid-diaphysis with a total cross-sectional tissue area reduced 43% relative to controls
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• at P28, tibias are about 22% shorter relative to controls
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• osteoblasts do not function properly, depositing abnormal collagen into the skeletal extracellular matrix
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Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| osteogenesis imperfecta | DOID:12347 |
OMIM:PS166200 |
J:211171 | |
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• 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
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• number of parvalbumin-containing Purkinje cells is only 43% of that in controls, however hippocampus and synaptic plasticity are normal
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• number of parvalbumin-positive interneurons in the molecular layer is decreased by 34.4%
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• exhibit substantially higher vertical activity, however no differences in the balance bar task, rotarod assay, or horizontal activity
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
| N |
• no significant differences in gastric epithelium relative to wild-type are observed at 1 month postnatal
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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 07/14/2026 MGI 6.24 |
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