A mutation in the Cdon gene potentiates congenital nevus development mediated by NRASQ61K |
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| Authors: | Arash Chitsazan Blake Ferguson Ramesh Ram Pamela Mukhopadhyay Herlina Y Handoko Brian Gabrielli Peter H Soyer Graeme J Walker |
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| Affiliation: | 1. QIMR Berghofer Medical Research Institute, Herston, QLD, Australia;2. The University of Queensland Diamantina Institute, Translational Research Institute, The University of Queensland (UQ), Brisbane, QLD, Australia;3. Centre for Diabetes Research, Harry Perkins Institute of Medical Research, Perth, WA, Australia;4. Dermatology Research Centre, UQ School of Medicine, Translational Research Institute, Brisbane, QLD, Australia |
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| Abstract: | Congenital nevi develop before birth and sometimes cover large areas of the body. They are presumed to arise from the acquisition of a gene mutation in an embryonic melanocyte that becomes trapped in the dermis during development. Mice bearing the Cdk4R24C::Tyr‐NRASQ61K transgenes develop congenital nevus‐like lesions by post‐natal day 10, from melanocytes escaping the confines of hair follicles. We interbred these mice with the collaborative cross (CC), a resource that enables identification of modifier genes for complex diseases (those where multiple genes are involved). We examined variation in nevus cell density in 66 CC strains and mapped a large‐effect quantitative trait locus (QTL) controlling nevus cell density to murine chromosome 9. The best candidate for a gene that exacerbates congenital nevus development in the context of an NRAS mutation is Cdon, a positive regulator of sonic hedgehog (Shh) that is expressed mainly in keratinocytes. |
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| Keywords: | Congenital nevi Qtl mice |
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