Analysis of this panel has located the CR hairless rat's hypotrichosis-generating mutation on chromosome 1, near Myl2, where only the fuzzy mutation in rat (fz) and the frizzy mutation in mouse (fr) have been previously localized. To determine if this mutation might be allelic (or orthologous) with any other previously mapped hypotrichosis-generating mutation in mammals, we have produced a panel of backcross rats segregating for the CR hairless rat mutation as well as numerous other markers from throughout the rat genome. Recent evidence has indicated that the recessive mutation affecting hypotrichosis in the Charles River (CR) " hairless" rat does not involve the hairless gene (hr) on rat chromosome 15. The Charles River " hairless" rat mutation maps to chromosome 1: allelic with fuzzy and a likely orthologue of mouse frizzy.Īhearn, K Akkouris, G Berry, P R Chrissluis, R R Crooks, I M Dull, A K Grable, S Jeruzal, J Lanza, J Lavoie, C Maloney, R A Pitruzzello, M Sharma, R Stoklasek, T A Tweeddale, J King, T R In vitro the dermis may require complete saturation before the diazepam can be detected in the receiving chamber These differences between the diffusion coefficients and diffusion rates (or permeability coefficients) suggest that the presence of the dermis may present some barrier properties.
#YOUNG MODEL SANDRA ORLOW NUDE SKIN#
Although human stratum corneum is almost twice the thickness of that of the hairless mouse, the diffusion coefficients for human skin were 3-12 times greater (0.76-3.31 X 10(-6) cm2/h for human skin vs 0.12-0.27 X 10(-6) cm2/h for hairless mouse) because of a shorter lag time for diffusion across human skin. The permeability coefficients for mouse skin ranged from 1.4-2.4 X 10(-2)cm/h compared with 0.8-1.4 X 10(-2)cm/h for human skin. Fluxes for mouse skin (stratum corneum, epidermis, and dermis) were greater than for human skin (stratum corneum and epidermis): 0.35-0.61 microgram/cm2/h for mouse skin vs 0.24-0.42 microgram/cm2/h for human skin. 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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