Study On The Biological Characteristics And Molecular Genetic Basis For The Yuyi Hairless Mice

The hairless gene is a crucial nuclear receptor gene associated with the structure of hair and skin. Itencodes a putative zinc finger transcription factor, and is a transcriptional corepressor for thyroid hormonereceptors. Hairless gene plays a critical role in maintaining the delicate balance between cell proliferation,differentiation, and apoptosis in the hair follicle as well as in the interfollicular epidermis, and is concernedwith the control of hair growth cycling. The hairless mouse resulted from hairless gene mutation showedabnormal structure of hair and skin, its phenotype resembles the human diseases know as papular atrichia(M1M 209500). Therefore the hairless mouse is a good experimental animal model. Yuyi hairless miceshowed progressive irreversible hair loss soon after birth, rhinocerotic appearance and shorter lifespan, werefirst reported in China, and were founded a segregated inbred strain. In contrast with KM mouse, bysystematic studies on phenotype, histopathology, ultrastructure, intron 6 of hairless gene, cDNA cloning,gene sequencing and functional analysis, we identified and reported a novel hairless mutant gene and fivepolymorphisms in hairless gene. Moreover, we studied the gene pleitrophism and genetic heterogeneity ofhairless gene by studying biological characteristics of hairless mouse carried hairless mutant gene, such asphenotype, skin history and ultrustructure et cetera. The primary results and conclusions were as follows.1. Studied the phenotype, skin histology and scanning electrochemical morphology of Yuyi hairless mice,and compared to haired littermates. It was shown that Yuyi hairless mice grew a first coat of hair andappeared normal until about 12 days after birth when loss of hair began periorbit, loss of hair progressed ina caudal direction. Except for vibrissae, hairless-like mutant mice developed alopecia after 2 weeks, grewno new hair, and the viscera were visible through the skin. With increased age, their skin becameprogressively thickened, loose and redundant, the skin of aged mouse formed rhinoceros-like folds andflaps, furthermore, the claws were noticeably elongated and tortuous, a waxy deposition and papules on theskin aging, the vibrissae were repeatedly shed and became shorter and sparser with age. Yuyi hairlessfemale and male mice were fertile, but most females displayed abnormalities in their maternal behavior, didnot nurse their young well. The thymus of mutant mice underwent accelerated atrophy with age. Thehomozygotes had reduced life span and usually expired at the age of 6-10 months. Histological evaluationof skin revealed homogeneous enlargement of utriculi, and the formation of several rows of large cysts.With electron microscope scanning, it could be found that the pilary canals of upper follicle first widenbefore shedding hair, and then lost their fur coat. At 2 months of age countless bubble or global-Iike substances on the skin surface in shape and size arranged in rows along the skin grooves. Pilary canals distended to be lenient utricles containing keratin fragments, and cysts in inequality of size appeared in dermis. At the age of 8 months the scale keratinized material substitute bubble-like substances, the skin grooves and ridges was exposed, dermis and subcutaneous tissue regressed, elastic fiber in a mess, and filled with several layer bigger cysts.2. Observed the gross morphology and ultrastructure of three congenic strains of hairless mice. It was shown that the procedure of shedding hair of three hairless congenic mice were similar to Yuyi hairless mouse. With increased age, the claws were noticeably elongated and twisted. BALB/c hairless mouse hadn't pigment deposition in skin, similar to Yuyi hairless mice. But DBA/2 and C57BL/6 hairless mice had pigment deposition in skin, and had darker pigment around orbit, snout, ear and tail. The naked skin contained numerous small white subcutaneous nodules of different size visible under the skin that gradually increased in size with age, and the vibrissae were repeatedly shed and became more abnormal and sparse with age. Further study of this mutant gene introduced into BALB/c strain by cross-intercross found a dominant characteristic of the shedding of hair on both side of the snout. This result validated the genetic heterogeneity of hairless gene. With electron microscope scanning, it could be found that the hair canals of upper follicle first widen before shedding hair. There was thicker keratinized squama material on skin surface of hairless mouse, hair follicles distended to be lenient cavity, and some follicles contained keratin fragments which sloughed onto the skin surface. The cysts could be seen at 35 days, and increased in size and quantity with age. Subcutaneous tissue regressed, and magnus cysts appeared apparently at 4 months of age.3. Cloning and sequencing of the entire cDNA encoding Hr from Kunming mouse were performed by RT-PCR method, and a full-length cDNA and CDS sequences of Kunming mouse were 4104bp and 3546bp, respectively, which has been accepted by GenBank (Accession Number: AY547391). Accession number of protein encoded by AY547391 sequence in GenBank is AAT45233 that is composed of 1181 amino acid residues. The Hr cDNA of Kunming mouse was cloned and sequenced for the first time. The identities of CDS of Hr gene were 99.9%, 94.4%, 83.1%, 78.1%, 81.9% and 82.1% by homologous comparison among Kunming mouse and other six species, and that were 99.9%, 92.2%, 81.7%, 70.8%, 79.9% and 80.1% respectively in amino acid sequences. The results suggested high degree of conservation and thus functional significance of the Hr gene among different mammalian taxons. The results derived from information...