title: A mutation in the serum and glucocorticoid-inducible kinase-like kinase (Sgkl) gene is associated with defective hair growth in mice.
abstract: YPC is a mutant mouse strain with defective hair growth characterized by thin, short hairs and poorly developed hair bulbs and dermal papillae. To identify the gene associated with the phenotype, we performed genome-wide linkage analysis using 1010 backcross progeny and 123 microsatellite markers covering all chromosomes. The mutant locus (ypc) was mapped to a 0.2-cM region in the proximal part of mouse chromosome 1. This 0.2-cM region corresponds to a 450-kb region of genome sequence that contains two genes with known functions and five ESTs or predicted genes with unknown functions. Sequence analysis revealed a single C-to-A nucleotide substitution at nucleotide 1382 in the Sgkl gene, causing a nonsense mutation at codon 461. Sgkl encodes serum and glucocorticoid-inducible kinase-like kinase (SGKL), which belongs to a subfamily of serine/threonine protein kinases and has been suggested to have a role downstream of lipid signals produced by activation of phosphoinositide 3-kinase (PI3K). In the mutant SGKL, a serine residue in the C-terminal end of the protein (Ser486), which is indispensable for activation of SGKL upon phosphorylation, is abolished by premature termination. Specific expression of the Sgkl gene in the inner root sheath of growing hair follicles was also identified by in situ hybridization. Therefore, we concluded that the nucleotide substitution in the Sgkl gene is the causative mutation for defective hair growth in the ypc mutant mouse and that the signaling pathway involving SGKL plays an essential role in mammalian hair development.
authors.affiliation: Graduate School of Natural Science and Technology, Okayama University, Tsushima-naka, Okayama, 700-8530, Japan.
authors.forename: Kentaro
authors.initials: K
authors.lastname: Masujin
authors.forename: Taro
authors.initials: T
authors.lastname: Okada
authors.forename: Takehito
authors.initials: T
authors.lastname: Tsuji
authors.forename: Yoshiyuki
authors.initials: Y
authors.lastname: Ishii
authors.forename: Kaoru
authors.initials: K
authors.lastname: Takano
authors.forename: Junichiro
authors.initials: J
authors.lastname: Matsuda
authors.forename: Atsuo
authors.initials: A
authors.lastname: Ogura
authors.forename: Tetsuo
authors.initials: T
authors.lastname: Kunieda
mesh_terms: D000818:Animals; D002874:Chromosome Mapping; D003001:Cloning, Molecular; D003062:Codon; D018389:Codon, Nonsense; D003433:Crosses, Genetic; D017931:DNA Primers / Q000737:chemistry; D018076:DNA, Complementary / Q000378:metabolism; D020224:Expressed Sequence Tags; D008040:Genetic Linkage; D016678:Genome; D005838:Genotype; D006197:Hair / Q000473:pathology*; D018859:Hair Follicle / Q000473:pathology; D006720:Homozygote; D017874:Immediate-Early Proteins; D017403:In Situ Hybridization; D050356:Lipid Metabolism; D051379:Mice; D018895:Microsatellite Repeats; D008957:Models, Genetic; D009154:Mutation; D009687:Nuclear Proteins / Q000235:genetics* / Q000378:metabolism; D010641:Phenotype; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases / Q000235:genetics* / Q000378:metabolism / Q000502:physiology*; D017434:Protein Structure, Tertiary; D012333:RNA, Messenger / Q000378:metabolism; D012694:Serine / Q000737:chemistry; D000099184:Serum-Glucocorticoid Regulated Kinases
chemical_list: D003062:Codon; D018389:Codon, Nonsense; D017931:DNA Primers; D018076:DNA, Complementary; D017874:Immediate-Early Proteins; D009687:Nuclear Proteins; D019869:Phosphatidylinositol 3-Kinases; D017346:Protein Serine-Threonine Kinases; D012333:RNA, Messenger; D012694:Serine; D000099184:Serum-Glucocorticoid Regulated Kinases; C503365:SGKL protein, mouse; C403243:SGK3 protein, human