Tissue-specific targeting of the pthrp gene: the generation of mice with floxed alleles. Endocrinology

PTH-related peptide (PTHrP) has been implicated in a variety of developmental and homeostatic processes. Although mice homozy-gous for the targeted disruption of the Pthrp gene have greatly ex-panded 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 b-actin promoter. The ubiquitous deletion of the floxe