This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Stem cells play a crucial role in adult tissue maintenance. Keratinocyte stem cells (KSCs) residing in the bulge region of the hair follicles (HFs) are responsible for the cyclic growth of the HFs and the maintenance of the epidermis upon wounding. In addition, KSCs also give rise to the sebaceous glands during HF morphogenesis. The rough coat (rc) arose spontaneously as a recessive mutation in C57BL/6J mice. Homozygous rc/rc mice are born indistinguishable from their normal littermates, but start to show unkempt hair coat and hair loss within a month after birth. Previous studies by our laboratory and others revealed sebaceous gland hypertrophy in these mice in addition to hair loss. These abnormalities may reflect a defect in KSC maintenance and differentiation. The rc locus was previously mapped to mouse chromosome 9, but the gene mutation remained to be identified. To better understand the biology of rc phenotype development, we characterized the skin and hair abnormalities in the rc/rc mice in more detail. We have shown that the hair loss in the rc/rc mice is cyclic and progressive. In addition, histological studies revealed that the sebaceous gland hypertrophy was due to sebocyte hyperplasia. Furthermore, we observed a high incidence of spontaneous and persistent skin lesions in rc/rc mice older than 10 months. To understand the genetic basis of rc phenotype development, we carried out positional cloning and identified a gene mutation in the rc/rc mice. Results from this study will shed new light on KSC fate determination and maintenance.
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