title: A mutation in the Cdon gene potentiates congenital nevus development mediated by NRAS(Q61K).
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 Cdk4(R24C) ::Tyr-NRAS(Q) (61K) 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.
authors.affiliation: QIMR Berghofer Medical Research Institute, Herston, QLD, Australia.|The University of Queensland Diamantina Institute, Translational Research Institute, The University of Queensland (UQ), Brisbane, QLD, Australia.
authors.forename: Arash
authors.initials: A
authors.lastname: Chitsazan
authors.affiliation: QIMR Berghofer Medical Research Institute, Herston, QLD, Australia.
authors.forename: Blake
authors.initials: B
authors.lastname: Ferguson
authors.affiliation: Centre for Diabetes Research, Harry Perkins Institute of Medical Research, Perth, WA, Australia.
authors.forename: Ramesh
authors.initials: R
authors.lastname: Ram
authors.affiliation: QIMR Berghofer Medical Research Institute, Herston, QLD, Australia.
authors.forename: Pamela
authors.initials: P
authors.lastname: Mukhopadhyay
authors.affiliation: QIMR Berghofer Medical Research Institute, Herston, QLD, Australia.
authors.forename: Herlina Y
authors.initials: HY
authors.lastname: Handoko
authors.affiliation: The University of Queensland Diamantina Institute, Translational Research Institute, The University of Queensland (UQ), Brisbane, QLD, Australia.
authors.forename: Brian
authors.initials: B
authors.lastname: Gabrielli
authors.affiliation: Dermatology Research Centre, UQ School of Medicine, Translational Research Institute, Brisbane, QLD, Australia.
authors.forename: Peter H
authors.initials: PH
authors.lastname: Soyer
authors.affiliation: Centre for Diabetes Research, Harry Perkins Institute of Medical Research, Perth, WA, Australia.
authors.forename: Grant
authors.initials: G
authors.lastname: Morahan
authors.affiliation: QIMR Berghofer Medical Research Institute, Herston, QLD, Australia.
authors.forename: Graeme J
authors.initials: GJ
authors.lastname: Walker
mesh_terms: D000818:Animals; D015815:Cell Adhesion Molecules / Q000235:genetics*; D002478:Cells, Cultured; D020405:Dermis / Q000378:metabolism / Q000473:pathology; D005260:Female; D020558:GTP Phosphohydrolases / Q000235:genetics*; D018859:Hair Follicle / Q000378:metabolism / Q000473:pathology; D006801:Humans; D015603:Keratinocytes / Q000378:metabolism / Q000473:pathology; D008297:Male; D008544:Melanocytes / Q000378:metabolism / Q000473:pathology*; D008565:Membrane Proteins / Q000235:genetics*; D051379:Mice; D018345:Mice, Knockout; D009154:Mutation; D009506:Nevus / Q000151:congenital* / Q000473:pathology; D012878:Skin Neoplasms / Q000151:congenital* / Q000473:pathology
chemical_list: C510744:Cdon protein, mouse; D015815:Cell Adhesion Molecules; D008565:Membrane Proteins; D020558:GTP Phosphohydrolases; C579846:NRAS protein, human
keywords: Congenital nevi; Qtl; mice