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. |