Gain of function p.E138A alteration in Card14 leads to psoriasiform skin inflammation and implicates genetic modifiers in disease severity.

John P Sundberg, The Jackson Laboratory
C Herbert Pratt, The Jackson Laboratory
Kathleen A Silva, The Jackson Laboratory
Victoria E. Kennedy, The Jackson Laboratory
Wenning Qin, The Jackson Laboratory
Timothy M Stearns, The Jackson Laboratory
Jacqueline Frost
Beth A. Sundberg, The Jackson Laboratory
Anne M Bowcock


Psoriasis (PS) is a common inflammatory and incurable skin disease affecting 2-3% of the human population. Although genome-wide association studies implicate more than 60 loci, the full complement of genetic factors leading to disease is not known. Rare, highly penetrant, gain-of-function, dominantly acting mutations within the human caspase recruitment domain family, member 14 (CARD14) gene lead to the development of PS and psoriatic arthritis (PSA) (a familial p.G117S and de-novo p.E138A alteration). These residues are conserved in mouse and orthologous Knock-In (KI) mutations within Card14 were created. The Card14