Flaky tail mice possess two distinct autosomal recessive mutations, hair abnormality (matted: ma) and stratum corneum layer abnormality (flaky tail: ft), and develop dermatitis spontaneously with high serum IgE even under specific pathogen free condition. We demonstrated that flaky tail mice possess loss of function mutation in Filaggrin (Flg) which is one of the major component of stratum corneum, and showed skin barrier abnormality, although our genetically engineered Flg null mice did not develop dermatitis spontaneously. As a result of segregation of ft and ma mutations, we identified that ma mutation is responsible for the dermatitis phenotype in flaky tail mice, and Tmem79 nonsense mutation (Tmem79(ma)) is corresponding to the ma mutation. Tmem79 is expressed in outermost cell of stratum granulosum layer, and ma mice showed abnormal lamellar granule secretory system and abnormal formation of stratum corneum. Thus, Tmem79(ma/ma) mice provides a useful mouse model for spontaneous dermatitis caused by skin barrier gene deficiency. Further analysis for Tmem79(ma/ma) mice would elucidate important mechanisms for development of atopic dermatitis.