Phenotypes Associated with This Genotype

Genotype
MGI:5546509

• Allelic Composition: Ctnnb1^tm1Mmt/Ctnnb1⁺; Tg(Msx2-rtTA)885Lma/0; Tg(tetO-cre)1Jaw/0
• Genetic Background: involves: 129 * 129X1/SvJ * C57BL/6

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

craniofacial

abnormal craniofacial morphology ( J:202618 )

• mutants on a doxycycline diet exhibit craniofacial malformations

integument

alopecia ( J:202618 )

• mutants on a doxycycline diet exhibit alopecia

mortality/aging

premature death ( J:202618 )

• 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

abnormal urinary bladder morphology ( J:202618 )

• 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

increased urinary bladder carcinoma incidence ( J:202618 )

• 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

neoplasm

increased urinary bladder carcinoma incidence ( J:202618 )

• 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		DO ID	OMIM ID(s)	Ref(s)
urinary bladder cancer		DOID:11054	OMIM:109800	J:202618