Fig. S5.

Interaction of Htt with Spink3 regulates trypsin activity in vitro. (A) Measurement of trypsin activity in vitro by adding Spink3, HTT, nHTT, tHTT, or Spink3 and HTT, nHTT, and tHTT containing cell lysates of transfected HEK293 cells. Cell extracts were mixed with porcine trypsin (TRSEQII) and the substrate Boc-Gln-Ala-Arg-AMC, and the rates of fluorescent products generated by trypsin were measured. Results are indicated as means ± SEM (n = 3; two-way ANOVA test, *P < 0.05, ***P < 0.001. (B) A model for Htt’s function in acinar cells. Htt binds Spink3 to inhibit trypsin activity in the pancreatic tissues in young mice. Loss of Htt will remove this inhibition, leading to trypsin activation in acinar cells and resulting in acinar cell degeneration and pancreas inflammation, as well as early death.