Transcript profiling of NLRP6 wild type and knockout mice

In both human and mouse, the NLRP6 sensor is translationally silenced outside of intestinal tissue. We find that alternative transcriptional promoters mediate this silencing in the mouse; a proximal promoter is employed outside of intestinal tissue that leads to expansion of the 5' leader sequence and abolishes translational efficiency by restricting nuclear export. Accordingly, Nlrp6 is dispensable in disease models of the kidney that expresses non-canonical isoforms. This results highlight alternative promoter use as a critical mechanism not just for isoform modulation, but for ultimately determining the expression profile and function of members of the pyrin-domain family of proteins.