About   Help   FAQ
Phenotypes associated with this allele
Allele Symbol
Allele Name
Allele ID
Trp63tm1Fmc
targeted mutation 1, Frank McKeon
MGI:1934269
Summary 7 genotypes
Jump to Allelic Composition Genetic Background Genotype ID
hm1
Trp63tm1Fmc/Trp63tm1Fmc involves: 129S2/SvPas * BALB/c MGI:3695126
hm2
Trp63tm1Fmc/Trp63tm1Fmc involves: 129S4/SvJae MGI:2174785
hm3
Trp63tm1Fmc/Trp63tm1Fmc involves: 129S4/SvJae * C57BL/6 MGI:4941055
ht4
Trp63tm1Fmc/Trp63+ involves: 129S4/SvJae MGI:3695136
ht5
Trp63tm1Fmc/Trp63+ involves: 129S4/SvJae * C57BL/6 MGI:5289945
cx6
Trp53tm1Tyj/Trp53+
Trp63tm1Fmc/Trp63+
involves: 129S2/SvPas * 129S4/SvJae * C57BL/6 MGI:5289961
cx7
Trp63tm1Fmc/Trp63+
Trp73tm1Fmc/Trp73+
involves: 129S4/SvJae * C57BL/6 MGI:5289956


Genotype
MGI:3695126
hm1
Allelic
Composition
Trp63tm1Fmc/Trp63tm1Fmc
Genetic
Background
involves: 129S2/SvPas * BALB/c
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Trp63tm1Fmc mutation (0 available); any Trp63 mutation (15 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
reproductive system
N
• oogenesis and folliculogenesis are essentially normal in mutants, when examined at E16.5 and E18.5




Genotype
MGI:2174785
hm2
Allelic
Composition
Trp63tm1Fmc/Trp63tm1Fmc
Genetic
Background
involves: 129S4/SvJae
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Trp63tm1Fmc mutation (0 available); any Trp63 mutation (15 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
mortality/aging
• mice die within 1 day of birth, from dessication and maternal neglect, secondary to developmental malformations

embryo
• recto-vaginal septum is absent, resulting in common cloacal opening
• from E9-12.5, limb buds are reduced and dysmorphic
• AER is absent and limb bud has only a simple, single-layered epithelium at distal tip
• at E9-12.5
• small, resulting in shortening of tail

craniofacial
• mice show dysmorphic craniofacial bone development
• mice have small, truncated mandibles compared to wild-type
• mice have small, truncated maxilla compared to wild-type
• secondary palate is truncated
• stratified squamous epithelium is replaced by 1-2 layers of cuboidal epithelial cells

limbs/digits/tail
• small, resulting in shortening of tail
• at E15, homozygotes lack distal components of the forelimb, including the radius, carpals and digits
• limb truncations due to failure to maintain the apical ectodermal ridge (AER)
• from E9-12.5, limb buds are reduced and dysmorphic
• AER is absent and limb bud has only a simple, single-layered epithelium at distal tip
• at E9-12.5
• at E15, homozygotes lack all components of the hindlimb

skeleton
• mice have small, truncated mandibles compared to wild-type
• mice have small, truncated maxilla compared to wild-type

digestive/alimentary system
• secondary palate is truncated
• stratified squamous epithelium is replaced by 1-2 layers of cuboidal epithelial cells
• there are abundant ciliated and goblet cells that are not seen in wild-type esophageal epithelium
• esophageal lining shows pseudostratified columnar appearance similar to respiratory epithelium
• recto-vaginal septum is absent, resulting in common cloacal opening
• 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
• 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
• mutants develop Barrett's-like metaplasia; origin of metaplasia is the primitive junctional epithelial cells of the squamocolumnar junction

endocrine/exocrine glands
• no prostatic ducts or epithelial budding structures are detected in the ventral or dorsolateral region of the periurethral mesenchyma, unlike in wild-type controls
• newborn males show absence of the prostate

renal/urinary system
• 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
• absent in some regions
• thinner than normal

reproductive system
• no prostatic ducts or epithelial budding structures are detected in the ventral or dorsolateral region of the periurethral mesenchyma, unlike in wild-type controls
• newborn males show absence of the prostate
• 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
• recto-vaginal septum is absent, resulting in common cloacal opening
• embryos demonstrate clitoral hypoplasia, due to absence of mature erectile tissue and overlying skin
• similar transfiguration as in stomach epithelium is observed
• similar transfiguration as in stomach epithelium is observed

vision/eye
• mutants have no eyelids at P1

cellular
• in the nasal epithelial at E11.5
• cells in remaining patches of epithelium on dermis have highly pyknotic nuclei, indicative of apoptosis

growth/size/body
• secondary palate is truncated
• stratified squamous epithelium is replaced by 1-2 layers of cuboidal epithelial cells

integument
• hair shafts are absent at P1
• no pelage follicles are present at P1
• 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)




Genotype
MGI:4941055
hm3
Allelic
Composition
Trp63tm1Fmc/Trp63tm1Fmc
Genetic
Background
involves: 129S4/SvJae * C57BL/6
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Trp63tm1Fmc mutation (0 available); any Trp63 mutation (15 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
digestive/alimentary system
• newborn homozygotes display abnormal persistence of ciliated cells in the esophageal epithelium
• however, budding from the foregut endoderm and tracheoesophageal separation occur normally
• 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

respiratory system
• 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
• neonatal tracheal epithelial lining consists of a well-organized, columnar ciliated epithelium that lacks basal cells, unlike in wild-type mice




Genotype
MGI:3695136
ht4
Allelic
Composition
Trp63tm1Fmc/Trp63+
Genetic
Background
involves: 129S4/SvJae
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Trp63tm1Fmc mutation (0 available); any Trp63 mutation (15 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
reproductive system
• upper genital tract is slightly smaller but structurally identical to wild-type
• slightly smaller but structurally identical to wild-type




Genotype
MGI:5289945
ht5
Allelic
Composition
Trp63tm1Fmc/Trp63+
Genetic
Background
involves: 129S4/SvJae * C57BL/6
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Trp63tm1Fmc mutation (0 available); any Trp63 mutation (15 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
respiratory system
• frequency of lung adenomas is 2.5 times that seen in wild-type mice

mortality/aging
• 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
• 40% of mutants exhibit increased signs of aging, developing severe degenerative disc disease of the spine between 6 and 18 months of age

neoplasm
• mutants show an increase in benign premalignant lesions such as squamous cell hyperplasia and multiple lung adenomas
• tumors undergo loss of heterozygosity
• frequency of lung adenomas is 2.5 times that seen in wild-type mice
• seen in 20% of mice by 12 months of age
• seen in 10% of mice by 12 months of age

skeleton
• 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




Genotype
MGI:5289961
cx6
Allelic
Composition
Trp53tm1Tyj/Trp53+
Trp63tm1Fmc/Trp63+
Genetic
Background
involves: 129S2/SvPas * 129S4/SvJae * C57BL/6
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Trp53tm1Tyj mutation (12 available); any Trp53 mutation (150 available)
Trp63tm1Fmc mutation (0 available); any Trp63 mutation (15 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
renal/urinary system
• 20% of mutants develop transitional cell carcinoma of the bladder

muscle
• 20% of mutants develop rhabdomyosarcomas

integument
• 10% of mutants develop mammary adenocarcinomas

endocrine/exocrine glands
• 10% of mutants develop mammary adenocarcinomas
• 10% of mutants develop thymic lymphomas

mortality/aging
• median age of survival is 7 months
• 40% of mutants exhibit increased signs of aging, developing severe degenerative disc disease of the spine between 6 and 18 months of age

neoplasm
• about 50% of mutants develop metastatic tumors
• 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
• 10% of mutants develop mammary adenocarcinomas
• 10% of mutants develop thymic lymphomas
• 20% of mutants develop rhabdomyosarcomas
• 15% of mutants develop myelogenous leukemia
• 50% of mutants develop squamous cell carcinomas in multiple tissues (larynx, pharynx, cervix, and esophagus)
• 20% of mutants develop transitional cell carcinoma of the bladder
• 20% of mutants develop osteosarcomas

skeleton
• 20% of mutants develop osteosarcomas
• 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




Genotype
MGI:5289956
cx7
Allelic
Composition
Trp63tm1Fmc/Trp63+
Trp73tm1Fmc/Trp73+
Genetic
Background
involves: 129S4/SvJae * C57BL/6
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Trp63tm1Fmc mutation (0 available); any Trp63 mutation (15 available)
Trp73tm1Fmc mutation (0 available); any Trp73 mutation (23 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
integument

digestive/alimentary system

endocrine/exocrine glands
• mutants that die by 6 months of age develop thymic lymphoma, hemangiosarcoma, or myelogenous leukemia

respiratory system

mortality/aging
• mutants survive for a shorter period of time than either single mutant, with some mutants dying by 6 months of age
• 60% of mutants exhibit increased signs of aging, developing severe degenerative disc disease of the spine between 6 and 18 months of age

neoplasm
• about 30% of mutants develop metastatic tumors
• tumors undergo loss of heterozygosity
• 50% of mutant mice have multiple tumors of the same or distinct types
• mutants that die by 6 months of age develop thymic lymphoma, hemangiosarcoma, or myelogenous leukemia
• mutants that die by 6 months of age develop myelogenous leukemia, thymic lymphoma, or hemangiosarcoma
• mice that die between 6 and 12 months of age most frequently develop carcinomas
• mutants that die by 6 months of age develop hemangiosarcoma, myelogenous leukemia, or thymic lymphoma

skeleton
• 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

behavior/neurological
• in 10% of mutants, degenerative disc disease is so severe, it results in partial paralysis





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)
Citing These Resources
Funding Information
Warranty Disclaimer & Copyright Notice
Send questions and comments to User Support.
last database update
10/01/2019
MGI 6.14
The Jackson Laboratory