1. ¹Life Sciences Division, Oak Ridge National Laboratory, Oak Ridge, Tennessee, USA
2. ²The Jackson Laboratory, Bar Harbor, Maine, USA
3. ³Center for Applied Genomics, Newark, New Jersey, USA
4. ⁴Genome Biology Division, Lawrence Livermore National Laboratory, Livermore, California, USA

Correspondence: Dr Brynn H. Voy, P.O. Box 2008, Oak Ridge, Tennessee 37831-6445, USA. E-mail: voybh@ornl.gov

Received 26 May 2006; Revised 3 October 2006; Accepted 31 October 2006; Published online 1 March 2007.

Abstract

Near-naked hairless (Hr^N) is a semi-dominant, spontaneous mutation that was suggested by allelism testing to be allelic with mouse Hairless (Hr). Hr^N mice differ from other Hr mutants in that hair loss appears as the postnatal coat begins to emerge, rather than as an inability to regrow hair after the first catagen and that the mutation displays semi-dominant inheritance. We sequenced the Hr cDNA in Hr^N/Hr^N mice and characterized the pathological and molecular phenotypes to identify the basis for hair loss in this model. Hr^N/Hr^N mice exhibit dystrophic hairs that are unable to emerge consistently from the hair follicle, whereas Hr^N/+ mice display a sparse coat of hair and a milder degree of follicular dystrophy than their homozygous littermates. DNA microarray analysis of cutaneous gene expression demonstrates that numerous genes are downregulated in Hr^N/Hr^N mice, primarily genes important for hair structure. By contrast, Hr expression is significantly increased. Sequencing the Hr-coding region, intron–exon boundaries, 5'- and 3'-untranslated region, and immediate upstream region did not reveal the underlying mutation. Therefore, Hr^N does not appear to be an allele of Hr but may result from a mutation in a closely linked gene or from a regulatory mutation in Hr.