Evaluating cornification in the dog by characterizing canine transglutaminase I and defining the clinical, histologic and morphometric features of normal, thyroxine-treated hypothyroid and untreated hypothyroid dogs.

摘要

Cornification is the process in which epithelial cells, called keratinocytes, mature to form the life-sustaining outer-most layer of the skin, the stratum corneum, and several components of the hair follicle including the hair shaft. Although cornification is a complex and highly regulated process, it always requires three elements: (1) structural proteins such as keratins, keratin-associated proteins, and the proteins that form the cell envelope, (2) lipids which act as a glue to aid in annealing proteins and (3) the action of enzymes known as transglutaminases that cross-link proteins and stabilize cell membranes.;In the first objective of the research described herein, a gene essential for normal cornification, the canine transglutaminase 1 ( tgm1) gene, was characterized by determining the sequence of its coding region, its putative amino acid sequence and its location within the canine genome using the polymerase chain reaction, fluorescence in situ hybridization and radiation hybrid mapping. This enzyme is central to the formation of the stratum corneum in all mammals and is a candidate cause for a number of inherited scaling skin diseases of dogs. The results show that canine tgm1 has a marked similarity to its human ortholog and is located on canine autosome 8.;The second objective of this dissertation was to define the differences in follicular cornification and hair growth in normal, thyroxine-treated hypothyroid and untreated hypothyroid Beagle dogs using morphologic and morphometric evaluation of the hair cycle and assessment of cell proliferation within the hair follicle by immunohistochemistry. These investigations demonstrated that the hair cycle of Beagle dogs is unlike that of the scalp hair of humans. Normal Beagles have a telogen-predominant hair growth pattern, meaning the majority of the hair follicles are in telogen, the resting stage of the hair cycle. In states of thyroid hormone deficiency, this resting stage becomes prolonged and when a telogen hair is eventually shed, it is not replaced, resulting in mild hair loss that differs from the classically described alopecia found in hypothyroidism. In thyroxine-treated hypothyroid dogs, telogen is still the predominant phase of the hair cycle, but the presence of many more anagen hairs suggests, as breeders have long believed, that thyroid hormone supplementation stimulates hair growth.;The morphologic changes that occur during the transition from telogen to anagen in canine hair follicles after hair shaft plucking were also examined in the three groups. Differences in the regeneration of plucked anagen and telogen follicles depended on the degree of injury that occurred at the time of plucking and the thyroid hormone state of the dog: hair follicles from untreated-hypothyroid dogs having the fewest hairs that regenerated. Importantly, unlike human and murine follicles, canine follicles do not demonstrate a localized area of proliferation within the follicle during the initiation of hair growth.