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Overexpression of Hoxc13 in differentiating keratinocytes results in downregulation of a novel hair keratin gene cluster and alopecia

Tkatchenko, A.V., Visconti, R.P., Shang, L.J., Papenbrock, T., Pruett, N.D., Ito, T., Ogawa, M. and Awgulewitsch, A. (2001) Overexpression of Hoxc13 in differentiating keratinocytes results in downregulation of a novel hair keratin gene cluster and alopecia Development, 128, (9), pp. 1547-1558.

Record type: Article


Studying the roles of Hox genes in normal and pathological development of skin and hair requires identification of downstream target genes in genetically defined animal models. We show that transgenic mice overexpressing Hoxc13 in differentiating keratinocytes of hair follicles develop alopecia, accompanied by a progressive pathological skin condition that resembles ichthyosis. Large-scale analysis of differential gene expression in postnatal skin of these mice identified 16 previously unknown and 13 known genes as presumptive Hoxc13 targets, The majority of these targets are downregulated and belong to a subgroup of genes that encode hair-specific keratin-associated proteins (KAPs).
Genomic mapping using a mouse hamster radiation hybrid panel showed these genes to reside in a novel KAP gene cluster on mouse chromosome 16 in a region of conserved linkage with human chromosome 21q22.11, Furthermore, data obtained by Hoxc13/lacZ reporter gene analysis in mice that overexpress Hoxc13 suggest negative autoregulatory feedback control of Hoxc13 expression levels, thus providing an entry point for elucidating currently unknown mechanisms that are required for regulating quantitative levels of Hox gene expression, Combined, these results provide a framework for understanding molecular mechanisms of Hoxc13 function in hair growth and development.

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Published date: May 2001
Keywords: Hoxc13, transgenic, target genes, alopecia, KAP gene cluster, mouse


Local EPrints ID: 35387
ISSN: 1477-9129
PURE UUID: 9e6d8604-4ad0-48ed-889c-da72edc28d1c

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Date deposited: 28 Jun 2006
Last modified: 17 Jul 2017 15:48

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Author: A.V. Tkatchenko
Author: R.P. Visconti
Author: L.J. Shang
Author: T. Papenbrock
Author: N.D. Pruett
Author: T. Ito
Author: M. Ogawa
Author: A. Awgulewitsch

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