Pinkie, the First Viable Germline Hypomorph Allele of Retinoid X Receptor Alpha, Reveals an Important Role for RXRa in Th2 Development.

The study focused on the Pinkie mutation, a recessive ENU-induced mutation in mice, which led to premature graying and progressive alopecia due to the destruction of hair follicle architecture. This mutation was mapped to the retinoid X receptor alpha (RXRa) locus and resulted in a hypomorphic allele with only 10 to 20% of the normal receptor activity. Pinkie homozygotes exhibited an imbalance in Th1/Th2 differentiation, with decreased IgG1 levels and altered cytokine production upon antigenic challenge. The findings suggested that RXRa played a crucial role in Th2 development, potentially influencing the expression of transcription factors and cytokines involved in immune response. The study implied that RXRa could link nutritional factors, such as retinoids and vitamin D, to immune status, offering insights into the rising prevalence of atopic diseases in developed countries.