Role of Aire and Notch4 allelic mutations in alopecia areata in C3H/HeJ mice

Human genetic association studies suggest that AIRE (autoimmune regulator gene) and NOTCH4 are directly associated with severe forms of alopecia areata, possibly distinct subtypes of the disease. To determine whether sequence variations in Aire or Notch4 affected onset or severity of alopecia areata in the well-established C3H/HeJ mouse model, 2 congenic strains C3.129S2(B6)-Aire (tm1.1Doi) /J (a null variant) and C3.129S1(B6)-Notch4 (tm1Grid) /J (a truncated allele expressing only the extracellular domain) were created. The congenic strains resulted in a decrease in the frequency of alopecia areata with Aire (tm1.1Doi) in the C3H/HeJ model. Close linkage to H2(b), a purported resistance gene, probably caused the C3.129S1(B6)-Notch4 (tm1Grid) /J to not develop any cases of alopecia areata.