Phenotypes associated with this allele

• Allele Symbol: Pkhd1^tm1Cjwa
• Allele Name: targeted mutation 1, Christopher J Ward
• Allele ID: MGI:3814174
• Summary: 3 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Pkhd1^tm1Cjwa/Pkhd1^tm1Cjwa	B6.129S6-Pkhd1^tm1Cjwa	MGI:3814177
hm2	Pkhd1^tm1Cjwa/Pkhd1^tm1Cjwa	C.129S6-Pkhd1^tm1Cjwa	MGI:3814176
hm3	Pkhd1^tm1Cjwa/Pkhd1^tm1Cjwa	involves: 129S6/SvEvTac * FVB/N	MGI:3814175

Genotype
MGI:3814177

hm1

• Allelic Composition: Pkhd1^tm1Cjwa/Pkhd1^tm1Cjwa
• Genetic Background: B6.129S6-Pkhd1^tm1Cjwa

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

renal/urinary system

dilated proximal convoluted tubule ( J:140302 )

• Background Sensitivity: dilation is detected in proximal tubules of congenic female mice by 3 months of age compared to 9 months of age in mice on a mixed background

Genotype
MGI:3814176

hm2

• Allelic Composition: Pkhd1^tm1Cjwa/Pkhd1^tm1Cjwa
• Genetic Background: C.129S6-Pkhd1^tm1Cjwa

renal/urinary system

kidney cyst ( J:140302 )

abnormal proximal convoluted tubule morphology ( J:140302 )

• attenuation of the brush border is seen in females that develop cystic changes at 3 months of age

dilated proximal convoluted tubule ( J:140302 )

• Background Sensitivity: dilation is detected in proximal tubules of congenic female mice by 3 months of age compared to 9 months of age in mice on a mixed background

growth/size/body

kidney cyst ( J:140302 )

Genotype
MGI:3814175

hm3

• Allelic Composition: Pkhd1^tm1Cjwa/Pkhd1^tm1Cjwa
• Genetic Background: involves: 129S6/SvEvTac * FVB/N

renal/urinary system

kidney cyst ( J:140302 )

♀ • females begin to develop cystic dilation in the outer stripe of the outer medulla and inner cortex at around 9 months of age

proximal convoluted tubule brush border loss ( J:140302 )

♀ • in older female mice in dilated tubules the brush border is attenuated or in extreme cases lost

♀ • in females at 9 months of age, surface blebs are seen on cilia and some cilia appear as branched clumps

♀ • in female mice at 15 months of age cilia on the lining of cysts are usually stunted and highly branched

dilated proximal convoluted tubule ( J:140302 )

♀ • dilation is confined to the proximal tubules in females at 9 - 15 months of age

♀ • dilation in females increases from 9 to 12 months of age

♀ • Background Sensitivity: dilation occurs later on a mixed background compared to congenic mice on either BALB/cJ or C57BL/6J backgrounds

♀ • dilation is not seen in males at up to 18 months of age

liver/biliary system

abnormal cholangiocyte primary cilium morphology ( J:140302 )

• primary cilia are shorter and often misshapen with multiple blebs in biliary trees affected by cystic changes

bile duct proliferation ( J:140302 )

• in early stages proliferation is seen in portal areas as primitive tortuous ducts and reactive stroma

dilated bile duct ( J:140302 )

• seen in all mice by 1 month of age

• worsens with age

abnormal liver morphology ( J:140302 )

liver cyst ( J:140302 )

• develop fibrocystic liver disease

• by 12 - 15 months of age, most of the liver is replaced with cysts

enlarged liver ( J:140302 )

• increase in the liver to body weight ratio by 9 months of age

• livers are often massively enlarged occupying much of the abdominal cavity

liver fibrosis ( J:140302 )

• develop fibrocystic liver disease

• by 6 - 9 months of age, portal fibrosis is evident

digestive/alimentary system

abnormal pancreatic duct morphology ( J:140302 )

• duct walls are thickened and lined with hyperplastic columnar epithelium

dilated pancreatic duct ( J:140302 )

• ducts are dilated

endocrine/exocrine glands

abnormal cholangiocyte primary cilium morphology ( J:140302 )

• primary cilia are shorter and often misshapen with multiple blebs in biliary trees affected by cystic changes

abnormal pancreatic duct morphology ( J:140302 )

• duct walls are thickened and lined with hyperplastic columnar epithelium

dilated pancreatic duct ( J:140302 )

• ducts are dilated

bile duct proliferation ( J:140302 )

• in early stages proliferation is seen in portal areas as primitive tortuous ducts and reactive stroma

dilated bile duct ( J:140302 )

• seen in all mice by 1 month of age

• worsens with age

pancreas cyst ( J:140302 )

• in some mice the pancreas is enlarged and markedly cystic

• dilated cysts are lined with hyperplastic columnar epithelium surrounded by fibrotic stroma

• microscopic cysts were seen in 44 of 92 mice

cellular

abnormal cholangiocyte primary cilium morphology ( J:140302 )

• primary cilia are shorter and often misshapen with multiple blebs in biliary trees affected by cystic changes

growth/size/body

pancreas cyst ( J:140302 )

• in some mice the pancreas is enlarged and markedly cystic

• dilated cysts are lined with hyperplastic columnar epithelium surrounded by fibrotic stroma

• microscopic cysts were seen in 44 of 92 mice

kidney cyst ( J:140302 )

♀ • females begin to develop cystic dilation in the outer stripe of the outer medulla and inner cortex at around 9 months of age

liver cyst ( J:140302 )

• develop fibrocystic liver disease

• by 12 - 15 months of age, most of the liver is replaced with cysts

enlarged liver ( J:140302 )

• increase in the liver to body weight ratio by 9 months of age

• livers are often massively enlarged occupying much of the abdominal cavity

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
autosomal recessive polycystic kidney disease		DOID:0110861		J:140302