TARGETED EXPRESSION OF SV40 T-ANTIGEN IN THE HAIR FOLLICLE OF TRANSGENIC MICE PRODUCES AN ABERRANT HAIR PHENOTYPE

Directed expression of SV40 large T antigen (TAg) in transgenic mice c an induce tissue-specific tumorigenesis and useful cell lines exhibiti ng differentiated characteristics can be established from resultant tu mor cells, In an attempt to produce an immortalised mouse hair follicl e cortical cell line for the study of hair keratin gene control, SV40 TAg expression was targeted to the hair follicles of transgenic mice u sing a sheep hair gene promoter, Expression of SV40 TAg in the follicl e cortex disrupted normal fiber ultrastructure, producing a marked phe notypic effect, Affected hairs were wavy or severely kinked (depending on the severity of the phenotype) producing an appearance ranging fro m a ruffled coat to a stubble covering the back of the mouse. The tran sgenic hairs appeared to be weakened at the base of the fibers, leadin g to premature hair-loss and a thinner pelage, or regions of temporary nudity, No follicle tumors or neoplasia were apparent and immortalisa tion of cortical cells could not be established in culture, In situ hy bridisation studies in the hair follicle using histone H3 as a cell pr oliferation marker suggested that cell proliferation had ceased prior to commencement of K2.10-TAg expression and was not re-established in the differentiating cortical cells, Hence, TAg was unable to induce ce ll immortalisation at that stage of cortical cell differentiation. How ever, transgenic mice developed various other abnormalities including vertebral abnormalities and bladder, liver and intestinal tumors, whic h resulted in reduced life expectancy.