Aa. Panteleyev et Am. Christiano, The Charles River "hairless" rat mutation is distinct from the hairless mouse alleles, COMPAR MED, 51(1), 2001, pp. 49-55
The Charles River (CR) "hairless" rat is one of the autosomal recessive hyp
otrichotic animal models actively studied in pharmacologic and dermatologic
research. Despite its widespread use, the molecular basis of this monogeni
c mutation remains unknown, and the skin histologic features of this phenot
ype have never been described. 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, We present a descripti
on of the histopathologic changes in heterozygous and homozygous CR hairles
s rat mutants during the first month of life, The postnatal homozygous rat
skin was characterized by abnormal keratinization of the hair shaft and for
mation of a thick and dense layer of corneocytes in the lower portion of th
e epidermal stratum corneum, This layer prevented the improperly keratinize
d hair shaft from penetrating the skin surface. Starting from the latest st
ages of hair follicle (HF) development, obvious signs of HF degeneration we
re observed in homozygous skin. This process was extremely rapid, and by da
y 12, mainly atrophic HFs with abnormal or broken hairs were present in the
skin. Therefore, the mutation in the CR rat abrogates eel proliferation in
the hair matrix and affects keratinocyte differentiation in the HF and int
erfollicular epidermis, a phenotype that is completely distinct from hr/hr,
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 evidenc
e that the hairless phenotype in CR rats is not allenic with hairless. Fina
lly, using intragenic polymorphisms, we were able to exclude homozygosity a
t the hairless locus by use of genotypic analysis. Thus, morphologic analys
is of successive stages of phenotype development in the CR hairless rat, to
gether with definitive molecular studies, indicate that this mutation may b
e unique among the other hypotrichotic rat mutations.