Mouse Genome Informatics
cn
    Ctnnb1tm1Mmt/Ctnnb1+
Tg(Msx2-rtTA)885Lma/0
Tg(tetO-cre)1Jaw/0

involves: 129 * 129X1/SvJ * C57BL/6
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
       
craniofacial
• mutants on a doxycycline diet exhibit craniofacial malformations

integument
• mutants on a doxycycline diet exhibit alopecia

mortality/aging
• 35% of mutants on a doxycycline diet for at least 3 weeks starting at P25 die during the 12 weeks following doxycycline administration; males and females die at similar rates

renal/urinary system
• urothelia of males on the doxycycline diet is more severely affected than in females
• increase in urothelial basal cell proliferation is seen in mutants fed doxycycline
• bladders of males 5 weeks after doxycline treatment show a higher proliferation index than females at the same stage

tumorigenesis
• 24% of the remaining surviving mutants on a doxycycline diet for at least 3 weeks starting at P25 exhibit tumors within the bladder lumen; 11 mutants have single tumor and 18 have multifoci tumors
• tumors in doxycline fed mutants resemble low-grade papillary urothelial carcinoma, exhibit polypoid structure, and the urothelium has lost its typical polarity and shows nuclear atypia, high mitogenic activity, and vascular infiltration
• however, no nuclear pleomorphism or muscle invasion is seen
• 45% of males on the doxycycline diet develop bladder tumors compared to 3% of females on the diet
• only 12.5% of castrated males after 3 months of doxycycline treatment develop luminal tumors and cell proliferation is 20% less than in noncastrated males

Mouse Models of Human Disease
OMIM IDRef(s)
Bladder Cancer 109800 J:202618