The Charles River "hairless" rat mutation is distinct from the hairless mouse alleles.
The Charles River "hairless" rat mutation is distinct from the hairless mouse alleles.
复制标题
查尔斯河“无毛”大鼠突变与无毛小鼠等位基因不同。
作者：
A. Panteleyev;A. Christiano
Charles River （CR）“无毛”大鼠是一种常染色体隐性少毛动物模型，在药理学和皮肤病学研究中得到了积极的研究。尽管其广泛使用，这种单基因突变的分子基础仍然未知，并且这种表型的皮肤组织学特征从未被描述过。然而，“无毛”的名称已被用作无毛小鼠（hr）命名法的延伸，基于两种表型的临床无毛。我们描述了杂合子和纯合子CR无毛大鼠突变体在出生后第一个月的组织病理学变化。出生后纯合子大鼠皮肤的特征是毛干角化异常，角质层下部形成厚而致密的角质层。这一层防止角化不当的毛干穿透皮肤表面。从毛囊发育的最后阶段开始，在纯合子皮肤中观察到明显的毛囊变性迹象。这个过程非常迅速，到第12天，皮肤上主要出现萎缩性hf，伴有异常或断裂的毛发。因此，CR大鼠的突变消除了毛基质中的细胞增殖，并影响了HF和毛囊间表皮的角化细胞分化，这是一种与hr/hr完全不同的表型。为了验证CR大鼠是否存在hr基因突变，我们分析了突变大鼠hr基因的编码区和内含子剪接位点的一致序列，未发现突变，进一步支持CR大鼠无毛表型与无毛不等位的表型证据。最后，利用基因内多态性，通过基因型分析，我们能够排除无毛位点的纯合性。因此，对CR无毛大鼠表型发育的连续阶段的形态学分析，以及明确的分子研究表明，这种突变可能是其他少毛大鼠突变中独特的。
The Charles River (CR) "hairless" rat is one of the autosomal recessive hypotrichotic animal models actively studied in pharmacologic and dermatologic research. 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. 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 description of the histopathologic changes in heterozygous and homozygous CR hairless rat mutants during the first month of life. 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. This layer prevented the improperly keratinized hair shaft from penetrating the skin surface. Starting from the latest stages of hair follicle (HF) development, obvious signs of HF degeneration were observed in homozygous skin. This process was extremely rapid, and by day 12, mainly atrophic HFs with abnormal or broken hairs were present in the skin. 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. 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. Finally, using intragenic polymorphisms, we were able to exclude homozygosity at the hairless locus by use of genotypic analysis. Thus, morphologic analysis of successive stages of phenotype development in the CR hairless rat, together with definitive molecular studies, indicate that this mutation may be unique among the other hypotrichotic rat mutations.