Phenotypes Associated with This Genotype

Genotype
MGI:5502373

• Allelic Composition: Pkd1^tm2Ggg/Pkd1^tm2Ggg; Tg(Col1a1-cre)1Bek/0
• Genetic Background: involves: 129S4/SvJae * CD-1

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

Pkd1^tm2Ggg/Pkd1^tm2Ggg Tg(Col1a1-cre)1Bek/0 mice develop polycystic pancreas and kidney

mortality/aging

premature death ( J:191967 )

• 50% mortality rate between birth and 6 months of age

postnatal lethality, incomplete penetrance ( J:191967 )

• 50% mortality rate between birth and 6 months of age

growth/size/body

pancreas cyst ( J:191967 )

• pancreatic cysts first become apparent at E15.5 and severe multiple cysts are seen by 6 weeks of age

• however, endocrine islet formation in pancreas is unaffected

polycystic kidney ( J:191967 )

• renal tubule cysts first become apparent at E15.5 and severe multiple cysts in the kidney are seen by 6 weeks of age

• however, glomeruli formation in the kidney is unaffected

decreased body size ( J:191967 )

decreased body weight ( J:191967 )

• at 6 weeks of age

renal/urinary system

polycystic kidney ( J:191967 )

• renal tubule cysts first become apparent at E15.5 and severe multiple cysts in the kidney are seen by 6 weeks of age

• however, glomeruli formation in the kidney is unaffected

renal fibrosis ( J:191967 )

• renal fibrosis of polycystic kidney starts at P7 and progressively becomes more severe by 6 weeks of age

endocrine/exocrine glands

abnormal exocrine pancreas morphology ( J:191967 )

• formation of pancreatic cysts lead to expansion of the pancreatic ducts and leads to massive acinar cell loss, formation of abnormal tubular structures, and appearance of endocrine cells in ducts

pancreas cyst ( J:191967 )

• pancreatic cysts first become apparent at E15.5 and severe multiple cysts are seen by 6 weeks of age

• however, endocrine islet formation in pancreas is unaffected

skeleton

abnormal osteoblast differentiation ( J:191967 )

• osteoblasts show impaired differentiation and maturation, as shown by culture duration-dependent reductions in ALP activity, diminished calcium deposition in extracellular matrix and a reduction in osteoblastic differentiation markers

increased osteoblast proliferation ( J:191967 )

• primary calvarial osteoblasts exhibit an increase in BrdU incorporation

short femur ( J:191967 )

• 17% shorter in length

abnormal bone marrow morphology ( J:191967 )

• number of adipocytes and fat droplets in tibia bone marrow are increased in 6 week old mutants

decreased bone mineral density ( J:191967 )

• adults exhibit severe osteopenia, with bone mineral density reduced by 35% and 36% in adult males and females, respectively

• however, newborns do not have skeletal abnormalities

decreased trabecular bone volume ( J:191967 )

• 73% reduction in trabecular bone volume

decreased compact bone thickness ( J:191967 )

• 41% reduction in cortical bone thickness

decreased bone mineralization ( J:191967 )

• periosteal mineral apposition rate is reduced by 41%

adipose tissue

abnormal adipose tissue development ( J:191967 )

• increase in adipogenesis in bone marrow and in bone marrow stromal cultures; higher number of adipocytes and volume of fat droplets in tibias

digestive/alimentary system

abnormal exocrine pancreas morphology ( J:191967 )

• formation of pancreatic cysts lead to expansion of the pancreatic ducts and leads to massive acinar cell loss, formation of abnormal tubular structures, and appearance of endocrine cells in ducts

cellular

abnormal osteoblast differentiation ( J:191967 )

• osteoblasts show impaired differentiation and maturation, as shown by culture duration-dependent reductions in ALP activity, diminished calcium deposition in extracellular matrix and a reduction in osteoblastic differentiation markers

increased osteoblast proliferation ( J:191967 )

• primary calvarial osteoblasts exhibit an increase in BrdU incorporation

homeostasis/metabolism

increased blood urea nitrogen level ( J:191967 )

• at 6 weeks of age

increased circulating parathyroid hormone level ( J:191967 )

• at 6 weeks of age

abnormal circulating mineral level ( J:191967 )

• levels of serum phosphorus are lower at 6 weeks of age

limbs/digits/tail

short femur ( J:191967 )

• 17% shorter in length

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
polycystic kidney disease 1		DOID:0110858	OMIM:173900	J:191967