Mice that are homozygous for this targeted mutation of Pkhd1 (polycystic kidney and hepatic disease 1) develop age progressive fibrocystic liver disease and cystic dilation of the kidney. Some homozygotes develop enlarged cystic pancreas. This mutant mouse strain may be useful in studies of Polycystic Kidney Disease.
Christopher J Ward, University of Kansas Medical Center
Mice that are homozygous for the targeted mutation are viable, fertile, normal in size and do not display any gross physical or behavioral abnormalities. A mutant gene product (mRNA), that skips exon 2 using the splice donor of exon 1 and the splice acceptor of exon 3, is detected by RT-PCR of kidney and liver tissue. By 9 months of age, homozygotes develop age progressive fibrocystic liver disease and cystic dilation of the kidney. Some homozygotes develop enlarged cystic pancreas. Histological analysis of females 3 months of age reveals dilated proximal convoluted tubules with attenuated brush border. This mutant mouse strain may be useful in studies of Polycystic Kidney Disease.
A targeting vector containing a floxed PGK-neo cassette was used to disrupt exon 2. The construct was electroporated into 129S6/SvEvTac derived TL-1 embryonic stem (ES) cells. Correctly targeted ES cells were injected into recipient blastocysts. The resulting chimeric animals were crossed to mice expressing Cre recombinase (GDF-9-iCre) on the C57BL/6 background to remove the floxed selection cassette. The mice were then backcrossed to C57BL/6J for 10 generations before being made homozygous.
|Allele Name||targeted mutation 1, Christopher J Ward|
|Allele Type||Targeted (Null/Knockout)|
|Gene Symbol and Name||Pkhd1, polycystic kidney and hepatic disease 1|
|Strain of Origin||129S6/SvEvTac|
|Molecular Note||A floxed neo cassette replaced exon 2 with a floxed neo cassette. The neo cassette was then removed via in vivo Cre mediated recombination. RT-PCR detected a transcript in mutants that skips exon 2 using the splice donor of exon 1 and the splice acceptor of exon 3.|
|Mutations Made By|| |
Christopher Ward, University of Kansas Medical Center
When maintaining a live colony, these mice can be bred as homozygotes.
When using the B6.129S6-Pkhd1tm1Cjwa/J mouse strain in a publication, please cite the originating article(s) and include JAX stock #009679 in your Materials and Methods section.