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This Article Full Text Full Text (PDF) Supplementary Figure for "A Functional Floxed Allele of Pkd1 ... Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Piontek, K. B. Articles by Germino, G. G. Search for Related Content PubMed PubMed Citation Articles by Piontek, K. B. Articles by Germino, G. G. Related Collections Related Article

A Functional Floxed Allele of Pkd1 that Can Be Conditionally Inactivated In Vivo

Klaus B. Piontek^*, David L. Huso, Alexander Grinberg, Lijuan Liu^*, Djahida Bedja, Haidan Zhao, Kathleen Gabrielson, Feng Qian^*, Changlin Mei, Heiner Westphal and Gregory G. Germino^*

Departments of *Medicine and Comparative Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland; Laboratory of Mammalian Genes and Development, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland; and Department of Medicine, Shanghai Changzheng Hospital, Shanghai, China

Correspondence to Dr. Gregory G. Germino, Johns Hopkins University School of Medicine, Departments of Medicine and Molecular Biology and Genetics, Division of Nephrology, Ross 958, 720 Rutland Avenue, Baltimore, MD 21205. Phone: 410-614-0089; Fax: 410-614-5129; E-mail: ggermino{at}jhmi.edu

Gene targeting has been used to create a variety of lines of mice with Pkd1 mutations that share many common features. Homozygous Pkd1 mutants invariably develop pancreatic and renal cysts if they survive to day 15.5 post coitum and die in either the fetal or the perinatal period. In contrast, mice with heterozygous mutations of Pkd1 are generally normal and have few if any renal cysts. These features have limited the utility of these models as tools to study the pathogenesis of cyst formation and the effect of various therapeutic interventions on disease progression. This report describes a new line of mice with a floxed allele of Pkd1 (Pkd1^cond) that has an FRT-flanked neomycin cassette inserted into intron 1 and lox P sites inserted into intron 1 and intron 4. The Pkd1^cond allele is fully functional, and homozygotes are viable and healthy. It is shown that the lox P and FRT sites can be selectively induced to recombine to produce two new alleles, Pkd1^del2–4 and Pkd1^cond-neo, by crossing to animals that express either the cre or FLPe recombinase, respectively. It is found that Pkd1^del2–4 allele functions as a true null, whereas presence or absence of the neomycin gene has no functional effects. It also is shown that somatic loss of Pkd1 results in renal and hepatic cysts. This new line of mice will be invaluable in the study of Pkd1 biology and serve as a powerful new tool that can be used to study the pathogenesis of autosomal dominant polycystic kidney disease.

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