Analysis Tools
reproductive system
| N |
• oogenesis and folliculogenesis are essentially normal in mutants, when examined at E16.5 and E18.5
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Allele Symbol Allele Name Allele ID |
Trp63tm1Fmc targeted mutation 1, Frank McKeon MGI:1934269 |
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| Summary |
7 genotypes
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
| N |
• oogenesis and folliculogenesis are essentially normal in mutants, when examined at E16.5 and E18.5
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• mice die within 1 day of birth, from dessication and maternal neglect, secondary to developmental malformations
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• recto-vaginal septum is absent, resulting in common cloacal opening
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• from E9-12.5, limb buds are reduced and dysmorphic
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• AER is absent and limb bud has only a simple, single-layered epithelium at distal tip
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• at E9-12.5
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• small, resulting in shortening of tail
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• mice show dysmorphic craniofacial bone development
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• mice have small, truncated mandibles compared to wild-type
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• mice have small, truncated maxilla compared to wild-type
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• secondary palate is truncated
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• stratified squamous epithelium is replaced by 1-2 layers of cuboidal epithelial cells
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• small, resulting in shortening of tail
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• at E15, homozygotes lack distal components of the forelimb, including the radius, carpals and digits
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• limb truncations due to failure to maintain the apical ectodermal ridge (AER)
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• from E9-12.5, limb buds are reduced and dysmorphic
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• AER is absent and limb bud has only a simple, single-layered epithelium at distal tip
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• at E9-12.5
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• at E15, homozygotes lack all components of the hindlimb
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• mice have small, truncated mandibles compared to wild-type
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• mice have small, truncated maxilla compared to wild-type
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• secondary palate is truncated
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• stratified squamous epithelium is replaced by 1-2 layers of cuboidal epithelial cells
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• there are abundant ciliated and goblet cells that are not seen in wild-type esophageal epithelium
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• esophageal lining shows pseudostratified columnar appearance similar to respiratory epithelium
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• recto-vaginal septum is absent, resulting in common cloacal opening
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• E18 fetuses exhibit a well-developed columnar epithelium in the proximal stomach rather than a mature squamous epithelium as in wild-type fetuses and exhibit markers of Barrett's esophagus
• E18 fetuses exhibit epithelial metaplasia in the proximal stomach
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• between E13 and E18, the proximal stomach epithelium undergoes a transition to a Barrett's-like metaplasia
• origin of the metaplasia is traced to a monolayer of Car4+cells that lie on the basement membrane of the proximal stomach and the Car4+ primitive epithelium of the stomach develops into a metaplasia after E14 because of the absence of an undermining population of squamous epithelium from the esophagus
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• mutants develop Barrett's-like metaplasia; origin of metaplasia is the primitive junctional epithelial cells of the squamocolumnar junction
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• no prostatic ducts or epithelial budding structures are detected in the ventral or dorsolateral region of the periurethral mesenchyma, unlike in wild-type controls
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• newborn males show absence of the prostate
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• mutants develop a bladder mucosa epithelial layer but fail to complete uroepithelial differentiation, producing a nontransitional default cuboidal epithelium
• mutants do not form the umbrella cells that make up the apical cell layer of the bladder epithelium
• mutants do not complete uroepithelial differentiation and thus do not develop the transitional epithelium but rather a nontransitional cuboidal epithelium
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• absent in some regions
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• thinner than normal
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• no prostatic ducts or epithelial budding structures are detected in the ventral or dorsolateral region of the periurethral mesenchyma, unlike in wild-type controls
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• newborn males show absence of the prostate
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• caudal structures are hypoplastic, with reduction in supporting connective tissue
• stratified squamous epithelium is absent on external genitalia, introitus, and vagina
• uterine Mullerian epithelium is contiguous with vaginal mucosa composed of urogenital and cloacal epithelia
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• recto-vaginal septum is absent, resulting in common cloacal opening
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• embryos demonstrate clitoral hypoplasia, due to absence of mature erectile tissue and overlying skin
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• similar transfiguration as in stomach epithelium is observed
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• similar transfiguration as in stomach epithelium is observed
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• mutants have no eyelids at P1
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• in the nasal epithelial at E11.5
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• cells in remaining patches of epithelium on dermis have highly pyknotic nuclei, indicative of apoptosis
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• secondary palate is truncated
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• stratified squamous epithelium is replaced by 1-2 layers of cuboidal epithelial cells
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• hair shafts are absent at P1
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• no pelage follicles are present at P1
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• stratified epidermis is absent, and basal, suprabasal and cornifed layer structures are lacking in mutants; late stage embryos and neonates retain isolated patches of disorganized epithelial cells along exposed dermis
(J:54637)
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Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| ectrodactyly, ectodermal dysplasia, and cleft lip-palate syndrome 3 | DOID:0060783 |
OMIM:604292 |
J:54637 | |
| gastroesophageal reflux disease | DOID:8534 |
OMIM:109350 |
J:173368 | |
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• newborn homozygotes display abnormal persistence of ciliated cells in the esophageal epithelium
• however, budding from the foregut endoderm and tracheoesophageal separation occur normally
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• neonatal esophageal epithelium consists largely of a highly organized, columnar ciliated epithelium that appears to lack K14+ basal cells, unlike in wild-type mice where several layers of cells with few ciliated cells and many K14+ basal cells are observed
• mutant ciliated cells make contact with the basement membrane, unlike cells in wild-type mice
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• neonatal tracheobronchial epithelium shows a significantly higher number of ciliated cells than in wild-type controls
• however, a trachea is formed suggesting that budding from the foregut endoderm and tracheoesophageal separation occur normally
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• neonatal tracheal epithelial lining consists of a well-organized, columnar ciliated epithelium that lacks basal cells, unlike in wild-type mice
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• upper genital tract is slightly smaller but structurally identical to wild-type
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• slightly smaller but structurally identical to wild-type
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• half of heterozygous mutants are moribound by 14-15 months of age
• by 2 years of age, 32 of 40 mutants had to be sacrificed or died
• mice die from not only the malignant lesions but also from the benign lesions due to such things as obstructed airways from hyperplastic or premalignant lesions in the pharynx, larynx, mouth or tongue
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• 40% of mutants exhibit increased signs of aging, developing severe degenerative disc disease of the spine between 6 and 18 months of age
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• mutants show an increase in benign premalignant lesions such as squamous cell hyperplasia and multiple lung adenomas
• tumors undergo loss of heterozygosity
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• frequency of lung adenomas is 2.5 times that seen in wild-type mice
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• seen in 20% of mice by 12 months of age
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• seen in 10% of mice by 12 months of age
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• 40% of mutants develop severe degenerative disc disease of the spine between 6 and 18 months of age
• degenerative disc disease is consistent with spondylosis and is most frequent in the cervical and thoracic region
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• frequency of lung adenomas is 2.5 times that seen in wild-type mice
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• median age of survival is 7 months
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• 40% of mutants exhibit increased signs of aging, developing severe degenerative disc disease of the spine between 6 and 18 months of age
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• about 50% of mutants develop metastatic tumors
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• mutants exhibit an increase in tumor burden compared to heterozygous Trp53 mice, with 90% of mutant mice having multiple tumors of the same or distinct types compared to only 10% in Trp53 heterozygotes
• mutants develop collision tumors composed of mammary adenocarcinomas directly adjacent to squamous cell carcinomas and/or rhabdomyosarcomas
• tumors exhibit loss of heterozygosity of one or both genes
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• 10% of mutants develop mammary adenocarcinomas
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• 10% of mutants develop thymic lymphomas
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• 20% of mutants develop rhabdomyosarcomas
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• 15% of mutants develop myelogenous leukemia
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• 50% of mutants develop squamous cell carcinomas in multiple tissues (larynx, pharynx, cervix, and esophagus)
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• 20% of mutants develop transitional cell carcinoma of the bladder
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• 20% of mutants develop osteosarcomas
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• 20% of mutants develop osteosarcomas
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• 40% of mutants develop severe degenerative disc disease of the spine between 6 and 18 months of age
• degenerative disc disease is consistent with spondylosis and is most frequent in the cervical and thoracic region
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• 10% of mutants develop mammary adenocarcinomas
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• 10% of mutants develop thymic lymphomas
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• 10% of mutants develop mammary adenocarcinomas
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• 20% of mutants develop rhabdomyosarcomas
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• 20% of mutants develop transitional cell carcinoma of the bladder
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• mutants survive for a shorter period of time than either single mutant, with some mutants dying by 6 months of age
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• 60% of mutants exhibit increased signs of aging, developing severe degenerative disc disease of the spine between 6 and 18 months of age
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• about 30% of mutants develop metastatic tumors
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• tumors undergo loss of heterozygosity
• 50% of mutant mice have multiple tumors of the same or distinct types
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• salivary adenoma
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• mutants that die by 6 months of age develop thymic lymphoma, hemangiosarcoma, or myelogenous leukemia
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• mutants that die by 6 months of age develop myelogenous leukemia, thymic lymphoma, or hemangiosarcoma
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• mice that die between 6 and 12 months of age most frequently develop carcinomas
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• mutants that die by 6 months of age develop hemangiosarcoma, myelogenous leukemia, or thymic lymphoma
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• 60% of mutants develop severe degenerative disc disease of the spine between 6 and 18 months of age
• degenerative disc disease is consistent with spondylosis and is most frequent in the cervical and thoracic region
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• in 10% of mutants, degenerative disc disease is so severe, it results in partial paralysis
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• salivary adenoma
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• mutants that die by 6 months of age develop thymic lymphoma, hemangiosarcoma, or myelogenous leukemia
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• salivary adenoma
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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 04/16/2024 MGI 6.23 |
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