title: Chk1 is essential for the development of murine epidermal melanocytes.
abstract: Embryonic deletion of mouse Chk1 is lethal; however, whether Chk1 is essential in all individual tissues is unknown. By breeding C57Bl/ 6 mice homozygous for a conditional allele of Chk1 (Chk1fl/fl) and bearing melanocyte-specific Tyr::Cre and DCT:: LacZ transgenes, we investigated the consequences of Chk1 deletion in the melanocytic lineage. We show that adult Tyr::Cre; Chk1fl/fl mice lack coat pigmentation and epidermal melanocytes in the hair follicles, but retain eye pigmentation in the retinal pigmented epithelium (RPE). Melanoblasts formed normally during embryogenesis in Tyr::Cre; Chk1fl/fl mice at early times (embryonic day 10.5; E10.5) but were completely absent by stage E13.5, most probably as a consequence of spontaneous DNA damage and apoptosis. By contrast, melanoblast numbers were only slightly reduced in heterozygous Tyr::Cre; Chk1fl/ + embryos, and these mice exhibited normal coat pigmentation as adults. Thus, Chk1 is essential for the developmental formation of murine epidermal melanocytes but hemizygosity has little, if any, permanent developmental consequence in this cell type.
authors.affiliation: Beatson Institute for Cancer Research, Glasgow, UK.
authors.forename: Joanne
authors.initials: J
authors.lastname: Smith
authors.forename: Lionel
authors.initials: L
authors.lastname: Larue
authors.forename: David A
authors.initials: DA
authors.lastname: Gillespie
mesh_terms: D000483:Alleles; D000818:Animals; D017209:Apoptosis; D016923:Cell Death; D000071877:Checkpoint Kinase 1; D004249:DNA Damage; D004817:Epidermis / Q000196:embryology* / Q000378:metabolism*; D004848:Epithelium / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental; D018859:Hair Follicle / Q000196:embryology; D006720:Homozygote; D007150:Immunohistochemistry; D008297:Male; D008544:Melanocytes / Q000166:cytology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008856:Microscopy, Fluorescence; D010858:Pigmentation; D011494:Protein Kinases / Q000235:genetics / Q000502:physiology*; D012168:Retinal Pigments / Q000378:metabolism; D013997:Time Factors
chemical_list: D012168:Retinal Pigments; D011494:Protein Kinases; D000071877:Checkpoint Kinase 1; C000605869:Chek1 protein, mouse