Phenotypes Associated with This Genotype

Genotype
MGI:5694081

• Allelic Composition: Hpse2^{Gt(OST411605)Lex}/Hpse2^{Gt(OST411605)Lex}
• Genetic Background: involves: 129S5/SvEvBrd * C57BL/6

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

mortality/aging

lethality at weaning, incomplete penetrance ( J:219597 )

• significant loss of homozygotes at 3 weeks of age

premature death ( J:219597 )

• remaining homozygotes die within one month after birth

growth/size/body

decreased body size ( J:219597 )

• at P18, homozygotes are noticeably smaller than wild-type controls

slow postnatal weight gain ( J:219597 )

• homozygotes exhibit reduced body weight gain during the first two weeks of life

weight loss ( J:219597 )

• homozygotes begin to lose weight after two weeks of age

renal/urinary system

renal/urinary system phenotype ( J:219597 )

N • homozygotes exhibit normal total glomeruli counts despite smaller kidney size

N • no signs of hydronephrosis, urinary tract inflammation, or vesicoureteral reflux are observed

increased urine protein level ( J:219597 )

• at P15-18

albuminuria ( J:219597 )

• at P15-18, urine albumin content and the urine albumin/creatinine ratio are significantly increased

small kidney ( J:219597 )

• mutant kidneys are significantly smaller but otherwise grossly normal

distended urinary bladder ( J:219597 )

• ~90% of homozygotes show distended bladders (megacystis)

• however, no obvious urethra stenosis is observed

urinary bladder fibrosis ( J:219597 )

• at P18, mutant bladders are palpably stiffer and show significantly increased collagen deposition, esp. within the interstitium of the detrusor layer, relative to wild-type controls

• however, no differences are noted at birth, when collagen deposition is minimal in both genotypes

abnormal urinary bladder physiology ( J:219597 )

• at P18, cell proliferation is significantly reduced within all bladder tissue layers, i.e. urothelium, lamina propria, and detrusor smooth muscle, as shown by Ki67 staining

• although Tgfbeta signaling is attenuated at P6, Tgfbeta activity is significantly enhanced at P18 (when excessive fibrotic tissue is observed), indicating pathological tissue remodeling in mutant bladders

• however, detrusor smooth muscle and urothelial cell fate determination are normal based on expression of specific molecular markers

abnormal urination pattern ( J:219597 )

• a VSOP (voided stain on paper) assay revealed that unrestrained homozygotes exhibit significantly smaller and more frequent urine spots (voids) than wild-type controls

increased urination frequency ( J:219597 )

• number of urine spots (voids) is significantly increased in a VSOP assay

urinary incontinence ( J:219597 )

• at P14-P18, cystometrogram (CMG) analysis showed that homozygotes leak constantly and have significantly higher resting and voiding intravesical pressures than wild-type controls

• occasionally, mutants cease to leak and show a concurrent steady increase in intravesical pressure until the reappearance of leaking/voiding

• the CMG pattern is highly irregular and the sharp spikes of acute increase of intravesical pressure are blunted

homeostasis/metabolism

decreased circulating glucose level ( J:219597 )

• at P15-18, blood glucose levels are significantly decreased

increased circulating alkaline phosphatase level ( J:219597 )

• at P15-18, blood ALP levels are significantly increased

decreased circulating serum albumin level ( J:219597 )

• at P15-18, blood albumin levels are significantly decreased

increased urine protein level ( J:219597 )

• at P15-18

albuminuria ( J:219597 )

• at P15-18, urine albumin content and the urine albumin/creatinine ratio are significantly increased

digestive/alimentary system

abnormal intestine morphology ( J:219597 )

• intestinal contents are grossly reduced, suggesting malnutrition and digestive tract defects

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
urofacial syndrome		DOID:0050816	OMIM:236730 OMIM:615112 OMIM:PS236730	J:219597