Phenotypes associated with this allele

• Allele Symbol: Trp63^tm1Fmc
• Allele Name: targeted mutation 1, Frank McKeon
• Allele ID: MGI:1934269
• Summary: 7 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Trp63^tm1Fmc/Trp63^tm1Fmc	involves: 129S2/SvPas * BALB/c	MGI:3695126
hm2	Trp63^tm1Fmc/Trp63^tm1Fmc	involves: 129S4/SvJae	MGI:2174785
hm3	Trp63^tm1Fmc/Trp63^tm1Fmc	involves: 129S4/SvJae * C57BL/6	MGI:4941055
ht4	Trp63^tm1Fmc/Trp63^+	involves: 129S4/SvJae	MGI:3695136
ht5	Trp63^tm1Fmc/Trp63^+	involves: 129S4/SvJae * C57BL/6	MGI:5289945
cx6	Trp53^tm1Tyj/Trp53^+ Trp63^tm1Fmc/Trp63^+	involves: 129S2/SvPas * 129S4/SvJae * C57BL/6	MGI:5289961
cx7	Trp63^tm1Fmc/Trp63^+ Trp73^tm1Fmc/Trp73^+	involves: 129S4/SvJae * C57BL/6	MGI:5289956

Genotype
MGI:3695126

hm1

• Allelic Composition: Trp63^tm1Fmc/Trp63^tm1Fmc
• Genetic Background: involves: 129S2/SvPas * BALB/c

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

reproductive system

reproductive system phenotype ( J:116176 )

N • oogenesis and folliculogenesis are essentially normal in mutants, when examined at E16.5 and E18.5

Genotype
MGI:2174785

hm2

• Allelic Composition: Trp63^tm1Fmc/Trp63^tm1Fmc
• Genetic Background: involves: 129S4/SvJae

mortality/aging

neonatal lethality, complete penetrance ( J:54637 )

• mice die within 1 day of birth, from dessication and maternal neglect, secondary to developmental malformations

embryo

abnormal septation of the cloaca ( J:79340 )

• recto-vaginal septum is absent, resulting in common cloacal opening

abnormal limb bud morphology ( J:54637 )

• from E9-12.5, limb buds are reduced and dysmorphic

absent apical ectodermal ridge ( J:54637 )

• AER is absent and limb bud has only a simple, single-layered epithelium at distal tip

small limb buds ( J:54637 )

• at E9-12.5

small tail bud ( J:79340 )

• small, resulting in shortening of tail

craniofacial

abnormal craniofacial morphology ( J:79340 )

• mice show dysmorphic craniofacial bone development

absent tooth placode ( J:54637 )

small mandible ( J:54637 )

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

small maxilla ( J:54637 )

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

abnormal secondary palate development ( J:54637 )

• secondary palate is truncated

absent tongue squamous epithelium ( J:54637 )

• stratified squamous epithelium is replaced by 1-2 layers of cuboidal epithelial cells

limbs/digits/tail

small tail bud ( J:79340 )

• small, resulting in shortening of tail

absent carpal bone ( J:54637 )

adactyly ( J:54637 )

abnormal forelimb morphology ( J:54637 )

• at E15, homozygotes lack distal components of the forelimb, including the radius, carpals and digits

absent radius ( J:54637 )

abnormal limb development ( J:54637 )

• limb truncations due to failure to maintain the apical ectodermal ridge (AER)

abnormal limb bud morphology ( J:54637 )

• from E9-12.5, limb buds are reduced and dysmorphic

absent apical ectodermal ridge ( J:54637 )

• AER is absent and limb bud has only a simple, single-layered epithelium at distal tip

small limb buds ( J:54637 )

• at E9-12.5

absent limbs ( J:79340 )

absent hindlimb ( J:54637 )

• at E15, homozygotes lack all components of the hindlimb

skeleton

absent tooth placode ( J:54637 )

small mandible ( J:54637 )

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

small maxilla ( J:54637 )

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

absent carpal bone ( J:54637 )

absent radius ( J:54637 )

digestive/alimentary system

abnormal secondary palate development ( J:54637 )

• secondary palate is truncated

absent tongue squamous epithelium ( J:54637 )

• stratified squamous epithelium is replaced by 1-2 layers of cuboidal epithelial cells

abnormal esophageal epithelium morphology ( J:54637 )

• there are abundant ciliated and goblet cells that are not seen in wild-type esophageal epithelium

abnormal esophageal squamous epithelium morphology ( J:54637 )

• esophageal lining shows pseudostratified columnar appearance similar to respiratory epithelium

rectovaginal fistula ( J:79340 )

♀ • recto-vaginal septum is absent, resulting in common cloacal opening

absent salivary gland ( J:54637 )

abnormal stomach epithelium morphology ( J:173368 )

• 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

abnormal stomach non-glandular epithelium morphology ( J:54637 )

gastric metaplasia ( J:173368 )

• 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

esophagogastric junction metaplasia ( J:173368 )

• mutants develop Barrett's-like metaplasia; origin of metaplasia is the primitive junctional epithelial cells of the squamocolumnar junction

endocrine/exocrine glands

absent salivary gland ( J:54637 )

absent mammary gland ( J:54637 )

♀

absent sebaceous gland ( J:54637 )

absent lacrimal glands ( J:54637 )

abnormal prostate gland branching morphogenesis ( J:66126 )

♂ • no prostatic ducts or epithelial budding structures are detected in the ventral or dorsolateral region of the periurethral mesenchyma, unlike in wild-type controls

absent prostate gland ( J:66126 )

♂ • newborn males show absence of the prostate

absent ovary ( J:79340 )

♀

renal/urinary system

abnormal urinary bladder urothelium morphology ( J:79341 )

• 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 urinary bladder urothelium ( J:54637 )

• absent in some regions

thin urinary bladder urothelium ( J:54637 )

• thinner than normal

reproductive system

abnormal prostate gland branching morphogenesis ( J:66126 )

♂ • no prostatic ducts or epithelial budding structures are detected in the ventral or dorsolateral region of the periurethral mesenchyma, unlike in wild-type controls

absent prostate gland ( J:66126 )

♂ • newborn males show absence of the prostate

abnormal female reproductive system morphology ( J:79340 )

♀ • 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

rectovaginal fistula ( J:79340 )

♀ • recto-vaginal septum is absent, resulting in common cloacal opening

absent ovary ( J:79340 )

♀

clitoris hypoplasia ( J:79340 )

♀ • embryos demonstrate clitoral hypoplasia, due to absence of mature erectile tissue and overlying skin

absent oviduct ( J:79340 )

♀

abnormal uterine cervix epithelium morphology ( J:54637 )

♀ • similar transfiguration as in stomach epithelium is observed

abnormal vagina epithelium morphology ( J:54637 )

♀ • similar transfiguration as in stomach epithelium is observed

vision/eye

absent lacrimal glands ( J:54637 )

absent eyelids ( J:54637 )

• mutants have no eyelids at P1

cellular

decreased apoptosis ( J:178316 )

• in the nasal epithelial at E11.5

increased apoptosis ( J:54637 )

• cells in remaining patches of epithelium on dermis have highly pyknotic nuclei, indicative of apoptosis

growth/size/body

absent tooth placode ( J:54637 )

abnormal secondary palate development ( J:54637 )

• secondary palate is truncated

absent tongue squamous epithelium ( J:54637 )

• stratified squamous epithelium is replaced by 1-2 layers of cuboidal epithelial cells

abnormal ventral body wall morphology ( J:79340 )

integument

absent mammary gland ( J:54637 )

♀

absent sebaceous gland ( J:54637 )

abnormal hair shaft morphology ( J:54637 )

• hair shafts are absent at P1

absent hair follicles ( J:54637 )

• no pelage follicles are present at P1

absent vibrissae ( J:54637 )

absent epidermis ( J:54637 , J:79340 )

• 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)

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

Genotype
MGI:4941055

hm3

• Allelic Composition: Trp63^tm1Fmc/Trp63^tm1Fmc
• Genetic Background: involves: 129S4/SvJae * C57BL/6

digestive/alimentary system

abnormal esophagus development ( J:95347 )

• newborn homozygotes display abnormal persistence of ciliated cells in the esophageal epithelium

• however, budding from the foregut endoderm and tracheoesophageal separation occur normally

abnormal esophageal squamous epithelium morphology ( J:95347 )

• 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

abnormal respiratory epithelium morphology ( J:95347 )

• 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

abnormal tracheal ciliated epithelium morphology ( J:95347 )

• 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: Trp63^tm1Fmc/Trp63⁺
• Genetic Background: involves: 129S4/SvJae

reproductive system

abnormal female reproductive system morphology ( J:79340 )

♀ • upper genital tract is slightly smaller but structurally identical to wild-type

small uterus ( J:79340 )

♀ • slightly smaller but structurally identical to wild-type

Genotype
MGI:5289945

ht5

• Allelic Composition: Trp63^tm1Fmc/Trp63⁺
• Genetic Background: involves: 129S4/SvJae * C57BL/6

mortality/aging

premature death ( J:98958 )

• 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

premature aging ( J:98958 )

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

neoplasm

increased tumor incidence ( J:98958 )

• mutants show an increase in benign premalignant lesions such as squamous cell hyperplasia and multiple lung adenomas

• tumors undergo loss of heterozygosity

increased lung adenoma incidence ( J:98958 )

• frequency of lung adenomas is 2.5 times that seen in wild-type mice

increased malignant tumor incidence ( J:98958 )

increased histiocytic sarcoma incidence ( J:98958 )

• seen in 20% of mice by 12 months of age

increased squamous cell carcinoma incidence ( J:98958 )

• seen in 10% of mice by 12 months of age

skeleton

intervertebral disk degeneration ( J:98958 )

• 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

respiratory system

increased lung adenoma incidence ( J:98958 )

• frequency of lung adenomas is 2.5 times that seen in wild-type mice

Genotype
MGI:5289961

cx6

• Allelic Composition: Trp53^tm1Tyj/Trp53⁺; Trp63^tm1Fmc/Trp63⁺
• Genetic Background: involves: 129S2/SvPas * 129S4/SvJae * C57BL/6

mortality/aging

premature death ( J:98958 )

• median age of survival is 7 months

premature aging ( J:98958 )

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

neoplasm

increased metastatic potential ( J:98958 )

• about 50% of mutants develop metastatic tumors

increased tumor incidence ( J:98958 )

• 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

increased T cell derived lymphoma incidence ( J:98958 )

• 10% of mutants develop thymic lymphomas

increased mammary adenocarcinoma incidence ( J:98958 )

• 10% of mutants develop mammary adenocarcinomas

increased rhabdomyosarcoma incidence ( J:98958 )

• 20% of mutants develop rhabdomyosarcomas

increased chronic myelocytic leukemia incidence ( J:98958 )

• 15% of mutants develop myelogenous leukemia

increased squamous cell carcinoma incidence ( J:98958 )

• 50% of mutants develop squamous cell carcinomas in multiple tissues (larynx, pharynx, cervix, and esophagus)

increased urinary bladder transitional cell carcinoma incidence ( J:98958 )

• 20% of mutants develop transitional cell carcinoma of the bladder

increased osteosarcoma incidence ( J:98958 )

• 20% of mutants develop osteosarcomas

skeleton

increased osteosarcoma incidence ( J:98958 )

• 20% of mutants develop osteosarcomas

intervertebral disk degeneration ( J:98958 )

• 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

endocrine/exocrine glands

increased T cell derived lymphoma incidence ( J:98958 )

• 10% of mutants develop thymic lymphomas

increased mammary adenocarcinoma incidence ( J:98958 )

• 10% of mutants develop mammary adenocarcinomas

integument

increased mammary adenocarcinoma incidence ( J:98958 )

• 10% of mutants develop mammary adenocarcinomas

muscle

increased rhabdomyosarcoma incidence ( J:98958 )

• 20% of mutants develop rhabdomyosarcomas

renal/urinary system

increased urinary bladder transitional cell carcinoma incidence ( J:98958 )

• 20% of mutants develop transitional cell carcinoma of the bladder

hematopoietic system

increased T cell derived lymphoma incidence ( J:98958 )

• 10% of mutants develop thymic lymphomas

immune system

increased T cell derived lymphoma incidence ( J:98958 )

• 10% of mutants develop thymic lymphomas

Genotype
MGI:5289956

cx7

• Allelic Composition: Trp63^tm1Fmc/Trp63⁺; Trp73^tm1Fmc/Trp73⁺
• Genetic Background: involves: 129S4/SvJae * C57BL/6

mortality/aging

premature death ( J:98958 )

• mutants survive for a shorter period of time than either single mutant, with some mutants dying by 6 months of age

premature aging ( J:98958 )

• 60% of mutants exhibit increased signs of aging, developing severe degenerative disc disease of the spine between 6 and 18 months of age

neoplasm

increased metastatic potential ( J:98958 )

• about 30% of mutants develop metastatic tumors

increased tumor incidence ( J:98958 )

• tumors undergo loss of heterozygosity

• 50% of mutant mice have multiple tumors of the same or distinct types

increased salivary gland adenoma incidence ( J:98958 )

• salivary adenoma

increased T cell derived lymphoma incidence ( J:98958 )

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

increased lung adenoma incidence ( J:98958 )

increased chronic myelocytic leukemia incidence ( J:98958 )

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

increased carcinoma incidence ( J:98958 )

• mice that die between 6 and 12 months of age most frequently develop carcinomas

increased mammary adenocarcinoma incidence ( J:98958 )

increased lung adenocarcinoma incidence ( J:98958 )

increased squamous cell carcinoma incidence ( J:98958 )

increased hemangiosarcoma incidence ( J:98958 )

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

skeleton

intervertebral disk degeneration ( J:98958 )

• 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

paralysis ( J:98958 )

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

endocrine/exocrine glands

increased salivary gland adenoma incidence ( J:98958 )

• salivary adenoma

increased T cell derived lymphoma incidence ( J:98958 )

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

increased mammary adenocarcinoma incidence ( J:98958 )

respiratory system

increased lung adenoma incidence ( J:98958 )

increased lung adenocarcinoma incidence ( J:98958 )

integument

increased mammary adenocarcinoma incidence ( J:98958 )

digestive/alimentary system

increased salivary gland adenoma incidence ( J:98958 )

• salivary adenoma

hematopoietic system

increased T cell derived lymphoma incidence ( J:98958 )

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

immune system

increased T cell derived lymphoma incidence ( J:98958 )

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

craniofacial

increased salivary gland adenoma incidence ( J:98958 )

• salivary adenoma

growth/size/body

increased salivary gland adenoma incidence ( J:98958 )

• salivary adenoma