Phenotypes Associated with This Genotype

Genotype
MGI:6251480

• Allelic Composition: Pkd2^tm1.1Gwu/Pkd2^tm1.1Gwu; Tg(Vil1-cre)997Gum/0
• Genetic Background: involves: C57BL/6 * C57BL/6J * SJL

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

mortality/aging

premature death ( J:265516 )

• most mice die between 4 and 6 months of age

• more than 50% of females survive to 5 months of age, approximately 1 month longer than males, indicating better survival for females

• treatment with rapamycin from P10 to P60 improves survival, with female rapamycin-treated mice having a median survival of about 7 months and male rapamycin-treated mice 6 months

• enhanced rapamycin treatment (extended duration) improves lifespan even more to a median survival of about 8 months

renal/urinary system

increased kidney cell proliferation ( J:265516 )

• mice show increased proliferation in renal epithelia

• rapamycin treatment suppresses the increased proliferation in renal epithelia

abnormal kidney morphology ( J:265516 )

• by 4 months of age, normal parenchyma is almost completely lost in the kidney

kidney cyst ( J:265516 )

• mice develop severe cysts in the kidneys

• renal cysts derive from all nephronic segments of the kidney

• renal cytogenesis is more severe in males than females

• treatment with rapamycin from P10 to P60 reduces growth of renal cysts, with treatment response better in females than males

• enhanced rapamycin treatment (extended duration) reduces renal cyst growth even more

enlarged kidney ( J:265516 )

• mice exhibit a larger kidney/body weight ratio by P15

kidney failure ( J:265516 )

endocrine/exocrine glands

pancreas cyst ( J:265516 )

• cysts in the pancreas are seen starting at 4 months of age

liver/biliary system

liver cyst ( J:265516 )

• cysts in liver are seen starting at 2 months of age with the cystic liver worsening rapidly with age

• however, the liver/body weight ratio and alanine aminotransferase levels are not different from wild-type

homeostasis/metabolism

increased circulating creatinine level ( J:265516 )

• mice show a higher creatinine level at 1 month of age

• creatinine levels are more elevated in males than in females at 4 months of age

• treatment with rapamycin improves creatinine levels but not completely to normal levels

• enhanced rapamycin treatment improves creatinine levels further

increased blood urea nitrogen level ( J:265516 )

• mice show a higher blood urea nitrogen level at 2 months of age

• blood urea nitrogen levels are more elevated in males than in females at 4 months of age

• treatment with rapamycin or enhanced rapamycin (extended duration) improves BUN levels to normal

cellular

increased kidney cell proliferation ( J:265516 )

• mice show increased proliferation in renal epithelia

• rapamycin treatment suppresses the increased proliferation in renal epithelia

growth/size/body

pancreas cyst ( J:265516 )

• cysts in the pancreas are seen starting at 4 months of age

kidney cyst ( J:265516 )

• mice develop severe cysts in the kidneys

• renal cysts derive from all nephronic segments of the kidney

• renal cytogenesis is more severe in males than females

• treatment with rapamycin from P10 to P60 reduces growth of renal cysts, with treatment response better in females than males

• enhanced rapamycin treatment (extended duration) reduces renal cyst growth even more

liver cyst ( J:265516 )

• cysts in liver are seen starting at 2 months of age with the cystic liver worsening rapidly with age

• however, the liver/body weight ratio and alanine aminotransferase levels are not different from wild-type

enlarged kidney ( J:265516 )

• mice exhibit a larger kidney/body weight ratio by P15

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
autosomal dominant polycystic kidney disease		DOID:898		J:265516