title: A functional floxed allele of Pkd1 that can be conditionally inactivated in vivo.
abstract: 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-Deltaneo), 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.
authors.affiliation: Department of Medicine, Division of Nephrology, Johns Hopkins University School of Medicine, 720 Rutland Avenue, Baltimore, MD 21205, USA.
authors.forename: Klaus B
authors.initials: KB
authors.lastname: Piontek
authors.forename: David L
authors.initials: DL
authors.lastname: Huso
authors.forename: Alexander
authors.initials: A
authors.lastname: Grinberg
authors.forename: Lijuan
authors.initials: L
authors.lastname: Liu
authors.forename: Djahida
authors.initials: D
authors.lastname: Bedja
authors.forename: Haidan
authors.initials: H
authors.lastname: Zhao
authors.forename: Kathleen
authors.initials: K
authors.lastname: Gabrielson
authors.forename: Feng
authors.initials: F
authors.lastname: Qian
authors.forename: Changlin
authors.initials: C
authors.lastname: Mei
authors.forename: Heiner
authors.initials: H
authors.lastname: Westphal
authors.forename: Gregory G
authors.initials: GG
authors.lastname: Germino
mesh_terms: D000483:Alleles; D000818:Animals; D004195:Disease Models, Animal; D007668:Kidney / Q000473:pathology; D008099:Liver / Q000473:pathology; D051379:Mice; D008817:Mice, Mutant Strains; D016254:Mutagenesis, Insertional / Q000379:methods*; D009355:Neomycin; D016891:Polycystic Kidney, Autosomal Dominant / Q000235:genetics* / Q000473:pathology / Q000503:physiopathology*; D011506:Proteins / Q000235:genetics* / Q000378:metabolism*; D050396:TRPP Cation Channels
chemical_list: D009355:Neomycin; D011506:Proteins; D050396:TRPP Cation Channels