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Peters, T.H.* ; Sedlmeier, R.* ; Büssow, H.* ; Runkel, F.* ; Lüers, G.H.* ; Korthaus, D.* ; Fuchs, H. ; Hrabě de Angelis, M. ; Stumm, G.* ; Russ, A.P.* ; Porter, R.M.* ; Augustin, M.A.* ; Franz, T.J.

Alopecia in a Novel Mouse Model RCO3 Is Caused by mK6irs1 Deficiency.

J. Invest. Dermatol. 121, 674-680 (2003)

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Reduced coat 3 (Rco3) is a new spontaneous autosomal recessive mutation with defects in hair structure and progressive alopecia. Here we describe chromosomal mapping and molecular identification of the Rco3 mutation. The murine Rco3 locus maps to a 2-Mb interval on chromosome 15 encompassing the keratin type II gene cluster. Recently, mK6irs1 was described as a type II keratin expressed in Henle's and Huxley's layer of the murine inner root sheath. Genomic sequencing revealed a 10-bp deletion in exon 1 of mK6irs1 resulting in a frameshift after 58 amino acid residues and, therefore, the absence of 422 carboxy-terminal amino acid residues containing the complete α-helical rod domain. Henle's and Huxley's layers show no immunoreactivity with mK6irs1-specific antibodies and the absence of intermediate filament formation in electron microscopic images. These results indicate that the expression of functional mK6irs1 is indispensable for intermediate filament formation in the inner root sheath and highlights the importance of the keratinization of the inner root sheath in the normal formation of the hair shaft.

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