Phenotypes Associated with This Genotype

Genotype
MGI:5789953

• Allelic Composition: Pten^tm2Mak/Pten^tm2Mak; Stk11^tm1Keis/Stk11^tm1Keis; Tg(Cyp1a1-cre/ERT)1Dwi/0
• Genetic Background: involves: 129P2/OlaHsd * C57BL/6 * C57BL/6J * CBA

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

Urothelial hyperplasia and increased apoptosis in bladder epithelium of Pten^tm2Mak/Pten^tm2Mak Stk11^tm1Keis/Stk11^tm1Keis Tg(Cyp1a1-cre/ERT)1Dwi/0 mice

mortality/aging

premature death ( J:169565 )

• mice injected with beta-napthoflavone and tamoxifen exhibit decreased survival after day 100 of induction, mostly due to bladder blockage

neoplasm

increased urinary bladder carcinoma incidence ( J:169565 )

• mice injected with beta-napthoflavone and tamoxifen develop large papillary bladder tumors by day 125 of induction

• tumor tissue shows signs of spindle-shaped cells, squamous metaplasia, focal microvesicular change, and increase in nuclear-cytoplasmic ratio

renal/urinary system

enlarged urinary bladder ( J:169565 )

• mice injected with beta-napthoflavone and tamoxifen exhibit enlarged bladders by 125 days of induction

• treatment with rapamycin reduces bladder size

increased urinary bladder carcinoma incidence ( J:169565 )

• mice injected with beta-napthoflavone and tamoxifen develop large papillary bladder tumors by day 125 of induction

• tumor tissue shows signs of spindle-shaped cells, squamous metaplasia, focal microvesicular change, and increase in nuclear-cytoplasmic ratio

abnormal urinary bladder mucosa morphology ( J:169565 )

• by day 100 of induction with beta-napthoflavone and tamoxifen, mucosa of bladders is thickened

abnormal urinary bladder urothelium morphology ( J:169565 )

• mice injected with beta-napthoflavone and tamoxifen exhibit urothelial hyperplasia by day 50 and 100 of induction

• bladder epithelium of beta-napthoflavone and tamoxifen treated mice shows presence of apoptosis and vacuoles at day 50 of induction

• elevation in proliferation in the urothelium of mice injected with beta-napthoflavone and tamoxifen

• marker analysis indicates that bladder urothelial cells of beta-napthoflavone and tamoxifen injected mice exhibit characteristics of epithelial-mesenchymal transition, with loss of epithelial markers and increases in mesenchymal markers

• treatment with rapamycin reduces urothelial epithelium thickness and suppresses the epithelial-to-mesenchymal transition

urinary bladder obstruction ( J:169565 )

• mice injected with beta-napthoflavone and tamoxifen show bladder obstruction due to tumors

growth/size/body

enlarged urinary bladder ( J:169565 )

• mice injected with beta-napthoflavone and tamoxifen exhibit enlarged bladders by 125 days of induction

• treatment with rapamycin reduces bladder size

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
urinary bladder cancer		DOID:11054	OMIM:109800	J:169565