Mouse Genome Informatics
hm
    Trp63tm2Brd/Trp63tm2Brd
involves: 129S7/SvEvBrd * C57BL/6J
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
       
mortality/aging
• death occurs within several hours of birth

embryogenesis
• at E11.5, both the mesenchyme and epithelium of the ventral UGS develop abnormally
• at E11.5, apoptosis is significantly increased in the ventral UGS epithelium, as determined by TUNEL assay and cleaved caspase-3 expression
• at E11.5, a reduction in cell proliferation is observed in the UGS mesenchyme relative to wild-type controls, as shown by BrdU staining
• small and misshapen at E11.5
• at E18.5, homozygotes with bladder exstrophy exhibit umbilical hernia

limbs/digits/tail
• small and misshapen at E11.5
• usually truncated, thinner than normal and deformed
• sometimes absent
• all are missing

skeleton
• usually truncated, thinner than normal and deformed
• sometimes absent
• all are missing
• pelvic girdle usually present but lacking ossification centers
• at E18.5, homozygotes with bladder exstrophy exhibit absence of pubic symphysis at the midline (i.e. separation of the pubic bones)

craniofacial
• "abnormal facies"

homeostasis/metabolism
• water loss occurs 30X more rapidly than in controls, a skin permeability problem

integument
• skin at birth totally lacks hair follicles
• reduced to a single layer of flattened cells
• epithelium of tongue and oral cavity is similar to the epidermis
• epidermal development apparently stops around E9.5
• water loss occurs 30X more rapidly than in controls, a skin permeability problem

renal/urinary system
• at E18.5, 4 of 12 homozygotes display bladder exstrophy with ventral bladder- and abdominal-wall defects (with and without membrane cover)
• the remaining 8 embryos develop dilated bladders with both thin lamina propria and thin muscle layers
• at E18.5, the lamina propria is either greatly reduced or absent
• at E18.5, 8 of 12 homozygotes exhibit dilated bladders with thin muscle layers
• at E14.5, premature smooth-muscle differentiation is observed relative to wild-type bladders
• at E18.5, little or no smooth muscle is detected ventrally, while a thin layer of smooth muscle is retained dorsally
• dorsal smooth muscle appears disorganized and non-stratified, unlike in wild-type bladders
• at E18.5, an abnormal bladder epithelium is observed along the dorso-ventral axis, with the dorsal epithelium consisting mainly of simple cuboidal cells and the ventral epithelium consisting primarily of simple squamous cells
• the ventral urothelium is neither committed to stratification nor differentiated, whereas the dorsal urothelium is both committed and differentiated
• at E11.5, a reduction in cell proliferation is observed in the ventral bladder epithelium and in adjacent mesenchyme relative to wild-type controls, as shown by BrdU staining
• at E12.5, an increase in ventral bladder epithelial apoptosis is associated with a transient upregulation of p53 and p73 expression
• at E12.5 and E13.5, developing bladders exhibit increased mitochondrial apoptotic activity relative to wild-type controls
• at E18.5, the bladder epithelium fails to differentiate into stratified transitional urothelium and remains as a single layer, unlike in wild-type controls
• at E18.5, 8 of 12 homozygotes develop dilated bladders with both thin lamina propria and thin muscle layers

reproductive system
• at E18.5, homozygotes with bladder exstrophy exhibit absence of external genitalia at the midline (i.e. bifid genitalia)
• separation of external genitalia is already noted at E11.5

growth/size
• "abnormal facies"
• at E18.5, 4 of 12 homozygotes display ventral abdominal wall defects

digestive/alimentary system
• at E18.5, homozygotes with bladder exstrophy exhibit ventral translocation of the anus

muscle
• at E18.5, 8 of 12 homozygotes exhibit dilated bladders with thin muscle layers
• at E14.5, premature smooth-muscle differentiation is observed relative to wild-type bladders
• at E18.5, little or no smooth muscle is detected ventrally, while a thin layer of smooth muscle is retained dorsally
• dorsal smooth muscle appears disorganized and non-stratified, unlike in wild-type bladders

cellular
• at E11.5, apoptosis is significantly increased in the ventral UGS epithelium, in skin overlying the urogenital tubercles, and in oral-cavity epithelium, as determined by TUNEL assay and/or cleaved caspase-3 expression
• at E12.5 and E13.5, developing bladders exhibit increased mitochondrial apoptotic activity, as revealed by increased expression of the mitochondrial apoptotic mediators

Mouse Models of Human Disease
OMIM IDRef(s)
Ectrodactyly, Ectodermal Dysplasia, and Cleft Lip/Palate Syndrome 3; EEC3 604292 J:54636
Exstrophy of Bladder 600057 J:119657