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Publication : Generation of Pmel-dependent conditional and inducible Cre-driver mouse line for melanocytic-targeted gene manipulation.

First Author  Nasrin M Year  2023
Journal  Pigment Cell Melanoma Res Volume  36
Issue  1 Pages  53-70
PubMed ID  36318272 Mgi Jnum  J:339313
Mgi Id  MGI:7520945 Doi  10.1111/pcmr.13074
Citation  Nasrin M, et al. (2023) Generation of Pmel-dependent conditional and inducible Cre-driver mouse line for melanocytic-targeted gene manipulation. Pigment Cell Melanoma Res 36(1):53-70
abstractText  Conditional and inducible gene targeting using Cre/loxP-mediated recombination is a powerful reverse genetics approach used to study spatiotemporal gene functions in specified cell types. To enable temporal gene manipulation in the melanocyte lineage, we established a novel inducible Cre-driver mouse line by targeting an all-in-one tetracycline/doxycycline (Dox)-inducible Cre expression cassette into the Pmel locus (Pmel(P2A-TetON3G-TRE3G-iCre) ), a gene locus preferentially expressed in pigment cells. By crossing these Cre-driver mice with a strong Cre-reporter mouse line, Gt(ROSA)26Sor(tm9(CAG-tdTomato)Hze) , we show the effectiveness of the Pmel(P2A-TetON3G-TRE3G-iCre) mouse line in facilitating Dox-inducible Cre/loxP recombination in a wide variety of pigment cell lineages including hair follicle melanocytes and their stem cells. Furthermore, to demonstrate proof of concept, we ablated Notch signaling postnatally in the Pmel(P2A-TetON3G-TRE3G-iCre) mice. In agreement with the previously reported phenotype, induced ablation of Notch signaling in the melanocyte lineage resulted in premature hair graying, demonstrating the utility of the Pmel(P2A-TetON3G-TRE3G-iCre) allele. Therefore, the Pmel(P2A-TetON3G-TRE3G-iCre) mouse line is suitable for assessing gene functions in melanocytes using an in vivo inducible reverse genetics approach. Furthermore, we unexpectedly identified previously unrecognized PMEL-expressing cells in non-pigmentary organs in the mice, suggesting unanticipated functions of PMEL other than melanosome formation.
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