Phenotypes Associated with This Genotype

Genotype
MGI:2654027

• Allelic Composition: Upk3a^tm1Tsun/Upk3a^tm1Tsun
• Genetic Background: either: (involves: 129S/SvEv) or (involves: 129S/SvEv * Swiss Webster)

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

Urothelium lacks the umbrella cells and is leaky in Upk3a^tm1Tsun/Upk3a^tm1Tsun mice

renal/urinary system

increased urine pH ( J:77653 )

• urine pH of about 15% of mutants is greater than or equal to 8 compared to 5-7 in wild-type

hydronephrosis ( J:77653 )

• renal pelvis of many mutants is enlarged with dilated collecting ducts and distal tubules, but minimally perturbed renal cortex

abnormal ureteral orifice morphology ( J:77653 )

• enlarged ureteral orifices, allowing backflow of urine

abnormal urothelium morphology ( J:77653 )

• urothelium is almost twice as thick as wild-type due to an increase in nuclear tiers four to five and does not posses a typical umbrella cell layer, showing a change of the superficial squamous cells to cuboidal or even columnar cells

• the apical cells of the urothelium are only 15-25 um in diameter compared to 150 um in wild-type, they frequently contract and detach, their cytoplasm lacks mature fusiform vesicles, and their apical surface is relatively smooth with abnormally small crystalline plaques interspersed by wide, particle-free hinge areas

• decrease in the surface area covered by urothelial plaques

vesicoureteral reflux ( J:77653 )

• vesicoureteral reflux pressure occurs at about 15 cm-H2O, which is significantly lower than in controls

abnormal urinary bladder physiology ( J:77653 )

• bladder is leaky to methylene blue

increased urination frequency ( J:77653 )

• mutants urinate almost twice as frequently as controls

homeostasis/metabolism

increased circulating creatinine level ( J:77653 )

• serum creatinine levels are 1.36 times higher than in controls

increased blood urea nitrogen level ( J:77653 )

• blood urea nitrogen levels are 1.4 times higher than in controls

increased urine pH ( J:77653 )

• urine pH of about 15% of mutants is greater than or equal to 8 compared to 5-7 in wild-type

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
vesicoureteral reflux		DOID:9620	OMIM:193000 OMIM:314550 OMIM:610878 OMIM:613674 OMIM:614317 OMIM:614318 OMIM:614319 OMIM:614674 OMIM:615390 OMIM:615963	J:77653