The type 1 diabetes candidate gene Dexi does not affect disease risk in the nonobese diabetic mouse model

Nieves-Bonilla, Janice, Badr Kiaf, Cornelia Schuster, and Stephan Kissler. 2019. “The Type 1 Diabetes Candidate Gene Dexi Does Not Affect Disease Risk in the Nonobese Diabetic Mouse Model”. Genes Immun.

Abstract

Genome-wide association studies have implicated more than 50 genomic regions in type 1 diabetes (T1D). A T1D region at chromosome 16p13.13 includes the candidate genes CLEC16A and DEXI. Conclusive evidence as to which gene is causal for the disease association of this region is missing. We previously reported that Clec16a deficiency modified immune reactivity and protected against autoimmunity in the nonobese diabetic (NOD) mouse model for T1D. However, the diabetes-associated SNPs at 16p13.13 were described to also impact on DEXI expression and others have argued that DEXI is the causal gene in this disease locus. To help resolve whether DEXI affects disease, we generated Dexi knockout (KO) NOD mice. We found that Dexi deficiency had no effect on the frequency of diabetes. To test for possible interactions between Dexi and Clec16a, we intercrossed Dexi KO and Clec16a knockdown (KD) NOD mice. Dexi KO did not modify the disease protection afforded by Clec16a KD. We conclude that Dexi plays no role in autoimmune diabetes in the NOD model. Our data provide strongly suggestive evidence that CLEC16A, not DEXI, is causal for the T1D association of variants in the 16p13.13 region.
Last updated on 03/07/2023