The juvenile alopecia mutation ( jal ) maps to mouse Chromosome 2, and is an allele of GATA binding protein 3 ( Gata3 )

Background Mice homozygous for the juvenile alopecia mutation ( jal ) display patches of hair loss that appear as soon as hair develops in the neonatal period and persist throughout life. Although a report initially describing this mouse variant suggested that jal maps to mouse Chromosome 13, our preliminary mapping analysis did not support that claim. Results To map jal to a particular mouse chromosome, we produced a 103-member intraspecific backcross panel that segregated for jal, and typed it for 93 PCR-scorable, microsatellite markers that are located throughout the mouse genome. Only markers from the centromeric tip of Chromosome 2 failed to segregate independently from jal , suggesting that jal resides in that region. To more precisely define jal ’s location, we characterized a second, 374-member backcross panel for the inheritance of five microsatellite markers from proximal Chromosome 2. This analysis restricted jal ’s position between D2Mit359 and D2Mit80 , an interval that includes Il2ra (for interleukin 2 receptor, alpha chain), a gene that is known to be associated with alopecia areata in humans. Complementation testing with an engineered null allele of Il2ra , however, showed that jal is a mutation in a distinct gene. To further refine the location of jal , the 374-member panel was typed for a set of four single-nucleotide markers located between D2Mit359 and D2Mit80 , identifying a 0.55 Mb interval where jal must lie. This span includes ten genes—only one of which, Gata3 (for GATA binding protein 3)—is known to be expressed in skin. Complementation testing between jal and a Gata3 null allele produced doubly heterozygous, phenotypically mutant offspring. Conclusions The results presented indicate that the jal mutation is a mutant allele of the Gata3 gene on mouse Chromosome 2. We therefore recommend that the jal designation be changed to Gata3 jal , and suggest that this mouse variant may provide an animal model for at least some forms of focal alopecia that have their primary defect in the hair follicle and lack an inflammatory component.