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Endocrinology Vol. 142, No. 5 2070-2077
Copyright © 2001 by The Endocrine Society

ARTICLES

Tissue-Specific Targeting of the Pthrp Gene: The Generation of Mice with Floxed Alleles1

Bin He, Ron A. Deckelbaum2, Dengshun Miao2, Mark L. Lipman3, Michael Pollak, David Goltzman and Andrew C. Karaplis2

Divisions of Endocrinology (B.H., R.A.D., A.C.K.) and Nephrology (M.L.L.), Department of Medicine, Department of Oncology (M.P.), and Lady Davis Institute for Medical Research, Sir Mortimer B. Davis-Jewish General Hospital, McGill University, Montréal, Québec, Canada H3T 1E2; and Calcium Research Laboratory (R.A.D., D.M., D.G.), Department of Medicine, Royal Victoria Hospital, McGill University, Montréal, Québec, Canada H3A 1A1

Address all correspondence and requests for reprints to: Andrew C. Karaplis, M.D., Ph.D., Lady Davis Institute for Medical Research, 3755 Côte Ste Catherine Road, Montréal, Québec, Canada H3T 1E2. E-mail: akarapli{at}ldi.jgh.mcgill.ca

PTH-related peptide (PTHrP) has been implicated in a variety of developmental and homeostatic processes. Although mice homozygous for the targeted disruption of the Pthrp gene have greatly expanded our capacity to investigate the developmental roles of the protein, the perinatal lethality of these animals has severely hindered the analysis of Pthrp’s postnatal physiological effects. To overcome this obstacle, we have generated mice homozygous for a floxed Pthrp allele, i.e. two loxP sites flanking exon 4 of the Pthrp gene, which encodes most of the protein, with the aim of accomplishing cell type- and tissue-specific deletion of the gene. The ability of the Cre enzyme to cause recombination between the loxP sites and excision of the intervening DNA sequence was tested in vivo by crossing this strain to mice carrying a cre transgene under the transcriptional control of the human ß-actin promoter. The ubiquitous deletion of the floxed allele in the cre/loxP progeny resulted in perinatal lethality as a consequence of aberrant endochondral bone formation, fully recapitulating all the phenotypic abnormalities observed in the conventional Pthrp knockout mouse. The availability of the floxed Pthrp mice will serve as a valuable tool in genetic experiments that aim to investigate the physiological actions of Pthrp in the postnatal state.




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