The observations above suggested that risk variants at the VPS13C locus may decrease the expression of nearby genes. To explore the potential impact of lowered VPS13C levels on insulin secretion, deletion of exon 1 (Fig. 3A) of the Vps13c gene was achieved throughout the pancreatic β-cell compartment in C57BL/6 mice from ∼E11.5 using the highly selective Ins1Cre deleter strain (69). As shown in Fig. 3, B and C, VPS13C was barely detected in islets isolated from βVps13cKO mice (Fig. 3B and Ci) and levels of Vps13c mRNA were significantly reduced (Fig. 3, Bii and Cii) by >80%. These findings are fully consistent with efficient (>94%) and exclusive (69) recombination in β-cells, which comprise 60–80% of the rodent islet (16), given that Vps13c mRNA is about twofold more abundant in β- than in α-cells (5), which comprise the majority of the islet non-β-cells. Expression of C2cd4a and C2cd4b in islets was variable between mice but was unaffected by Vps13c deletion. Changes in body weight gain (Fig. 3, D and E) and random-fed glycemia (Fig. 3, F and G) over time were not different between control (Ctrl) and βVps13cKO (KO) mice irrespective of sex or diet [regular chow (RC) vs. high-fat diet (HFD); see materials and methods for details].