VESICLE FORMATION AND FOLLICULAR ROOT SHEATH SEPARATION IN MICE HOMOZYGOUS FOR DELETERIOUS ALLELES AT THE BALDING (BAL) LOCUS

The balding (bal) mutation of the mouse is an autosomal recessive muta tion that causes alopecia and immunologic anomalies. A new allele was identified by allelism testing after using an interspecific backcross to localize the mutation to the centromeric end of mouse chromosome 18 . We investigated the skin and hair histologic lesions of two alleles (bal(J) and bal(Pas)) at this locus and analyzed the expression of sev eral keratinocyte markers and the production of autoantibodies by immu nofluorescence on frozen skin sections. The lesions observed included separation of the inner and outer root sheath in anagen follicles resu lting in the hair fiber being very easily plucked from the follicle. V esicles on the ventral tongue, mucocutaneous junction of the eyelid, f oot pads, and rarely in skin were also evident. Separation occurred be tween the basal and suprabasilar cells forming an empty cleft, resembl ing that observed in human pemphigus vulgaris. Immunofluorescence stud ies did not reveal the presence of tissue-bound or circulating autoant ibodies. Expression of keratinocyte markers in hair follicles was norm al. Keratin 6-positive cells were found on either side of the follicul ar separation suggesting a molecular defect in adhesion molecules betw een the inner layer of the outer root sheath cells to layers on either sides. This hypothesis has been confirmed by another group who demons trated that the bal(J) mutation is due to the insertion of a thymidine in the desmoglein 3 gene, resulting in a premature stop codon.