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Melanocyte-lineage expression of Cre recombinase using Mitf regulatory elements.

Pigment cell & melanoma research | 2008

Manipulation of gene expression in melanocytes is an important tool for studying pigment cell biology. We constructed transgenic mice in which Cre recombinase was placed under the control of regulatory elements from the Microphthalmia-associated transcriptional factor (Mitf) gene using bacterial artificial chromosome (BAC). Bacterial artificial chromosome that contained either 50 or 108 kb DNA 5' to the melanocyte-specific (1M) transcriptional start site gave rise to transgenic lines in which Cre is expressed specifically in cells of the melanocyte lineage, as judged by activation of the Gt(Rosa)26(tm1Sor)(R26R) reporter locus. Activation of R26R is first detectable in melanoblasts of midgestation embryos, and completely marks all melanocyte components of the skin in postnatal animals. To test the utility of the MitfCre transgene, we used a loxP-targeted allele of the protein kinase A alpha catalytic subunit (Prkaca), modified such that Cre-mediated recombination activates PKA signaling. On an agouti background, animals carrying both the MitfCre transgene and the targeted Prkaca allele (CalphaR) exhibited a darker coat color than control littermates, due to a shift from pheomelanin to eumelanin synthesis. Our results confirm that PKA signaling is a key component of pigment type-switching, and provide a new tool for studying pigment cell biology.

Pubmed ID: 18353144 RIS Download

Mesh terms: Animals | Cell Lineage | Chromosomes, Artificial, Bacterial | Cyclic AMP-Dependent Protein Kinase Catalytic Subunits | Gene Expression Regulation, Developmental | Genotype | Hair Color | Integrases | Melanins | Melanocytes | Mice | Mice, Inbred C57BL | Mice, Inbred CBA | Mice, Transgenic | Microphthalmia-Associated Transcription Factor | Phenotype | Proteins | RNA, Untranslated | Recombination, Genetic | Regulatory Elements, Transcriptional | Signal Transduction