Mouse Genome Informatics
hm
    Trp63tm1Fmc/Trp63tm1Fmc
involves: 129S4/SvJae
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
       
mortality/aging
• mice die within 1 day of birth, from dessication and maternal neglect, secondary to developmental malformations

embryogenesis
• 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 (J:79340)
• 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
(J:79340)
• no prostatic ducts or epithelial budding structures are detected in the ventral or dorsolateral region of the periurethral mesenchyma, unlike in wild-type controls (J:66126)
• newborn males show absence of the prostate (J:66126)

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

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 (J:66126)
• newborn males show absence of the prostate (J:66126)
• caudal structures are hypoplastic, with reduction in supporting connective tissue (J:79340)
• stratified squamous epithelium is absent on external genitalia, introitus, and vagina (J:79340)
• uterine Mullerian epithelium is contiguous with vaginal mucosa composed of urogenital and cloacal epithelia (J:79340)
• recto-vaginal septum is absent, resulting in common cloacal opening (J:79340)
(J:79340)
• embryos demonstrate clitoral hypoplasia, due to absence of mature erectile tissue and overlying skin (J:79340)
(J:79340)
• similar transfiguration as in stomach epithelium is observed (J:54637)
• similar transfiguration as in stomach epithelium is observed (J:54637)

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

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)

Mouse Models of Human Disease
OMIM IDRef(s)
Ectrodactyly, Ectodermal Dysplasia, and Cleft Lip/Palate Syndrome 3; EEC3 604292 J:54637
Gastroesophageal Reflux; GER 109350 J:173368