The variation in diffusion rate or the flux for both human and mouse tissues was greater among specimens than between duplicate or triplicate trials for a single specimen. Diazepam was found to diffuse across human and hairless mouse skin unchanged in experiments with twin-chambered diffusion cells. Diazepam was readily absorbed after topical administration to the intact hairless mouse, a total of 75.8% of the 14 C-label applied being recovered in urine and feces. The objectives of this study were to investigate the absorption of diazepam applied topically to the hairless mouse in vivo and to determine the diffusion of diazepam across isolated hairless mouse skin and human skin. International Nuclear Information System (INIS) Thus, morphologic analysis of successive stages of phenotype development in the CR hairless rat, together with definitive molecular studiesĭiffusion of diazepam across hairless mouse skin and human skin Finally, using intragenic polymorphisms, we were able to exclude homozygosity at the hairless locus by use of genotypic analysis. To test whether the CR rat harbored a mutation in the hr gene, we analyzed the coding region of this gene and consensus intron splice site sequences in mutant rats and found no mutation, further supporting phenotypic evidence that the hairless phenotype in CR rats is not allelic with hairless. Therefore, the mutation in the CR rat abrogates cell proliferation in the hair matrix and affects keratinocyte differentiation in the HF and interfollicular epidermis, a phenotype that is completely distinct from hr/hr. This process was extremely rapid, and by day 12, mainly atrophic HFs with abnormal or broken hairs were present in the skin.

Starting from the latest stages of hair follicle (HF) development, obvious signs of HF degeneration were observed in homozygous skin. This layer prevented the improperly keratinized hair shaft from penetrating the skin surface. The postnatal homozygous rat skin was characterized by abnormal keratinization of the hair shaft and formation of a thick and dense layer of corneocytes in the lower portion of the epidermal stratum corneum. We present a description of the histopathologic changes in heterozygous and homozygous CR hairless rat mutants during the first month of life. However, the designation ' hairless' has been used as an extension of the hairless mouse (hr) nomenclature on the basis of the clinical absence of hairs in both phenotypes. Despite its widespread use, the molecular basis of this monogenic mutation remains unknown, and the skin histologic features of this phenotype have never been described. The Charles River (CR) ' hairless' rat is one of the autosomal recessive hypotrichotic animal models actively studied in pharmacologic and dermatologic research.

The Charles River ' hairless' rat mutation is distinct from the hairless mouse alleles.

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