International Mammalian Genome Society

logo18th International Mouse Genome Conference

17-22 October 2004, Seattle, USA


POSTER 114 -  A MUTATION IN THE SERUM AND GLUCOCORTICOID-INDUCIBLE KINASE-LIKE KINASE (SGKL) GENE IS RESPONSIBLE FOR DEFECTIVE HAIR GROWTH IN MICE

Masujin K 1, Okada T 2, Izawa N 1, Tuji T 1, Ishii Y 2, Takano K 3, Matsuda J 3, Ogura A 4, Kunieda T 1

1 Graduate School of Natural Science and Technology, Okayama University, Okayama, Japan, 2 Graduate School of Agricultural and Life Sciences, The University of Tokyo, Tokyo, Japan, 3 National Institute of Infectious diseases, Tokyo, Japan, 4 RIKEN Bioresource Center, Ibaraki, Japan

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 responsible for the phenotype, we performed genome-wide linkage analysis using 1,010 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 1,382 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 mutation in the Sgkl gene is responsible for defective hair growth in the ypc mutant mouse and that the signaling pathway involving SGKL plays an essential role in mammalian hair development.  We also found a single nucleotide insertion in the Sgkl gene of fz mouse that is another mutant mouse showing hair abnormalities resembling to that of YPC mouse.  The nucleotide insertion causes a frame shift mutation in the middle part of the protein.

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