B6.129S6-Pkhd1^tm1Cjwa/J

Stock number: 009679
Product name: Pkhd1^del2 (exon 2 deleted; KO)
Research areas: Internal/Organ Research

Description

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.

Detailed description

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.

Development

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

Symbol: Pkhd1^tm1Cjwa
Name: targeted mutation 1, Christopher J Ward
MGI accession ID: MGI:3814174
Generation method: Targeted
Attributes: Null/Knockout
Synonyms: Pkhd1^del2
Marker symbol: Pkhd1
Marker name: polycystic kidney and hepatic disease 1
Marker synonyms: AABR07067023.1; ARPKD; FCYT; FPC; PCYT; PKD4; TIGM1; tigmin
Chromosome: 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.