HSD17B13 is a liver lipid droplet-associated enzyme that interacts with steroid substrates, bioactive lipids, and retinol. Three unique HSD17B13 genetic variants have been discovered that offer protection against harm in NASH, alcoholic liver disease, and hepatocellular carcinoma. The exons 1-7 of mouse Hsd17b13 gene that encode the whole molecule were replaced by human counterparts in B-hHSD17B13 mice. The promoter, 5’UTR and 3’UTR region of the mouse gene are replaced by human counterparts. Human HSD17B13 mRNA was detectable only in homozygous B-hHSD17B13 mice, but not in wild-type C57BL/6 mice. HSD17B13 protein was detectable in kidney, liver and stomach of wild-type C57BL/6 mice and homozygous B-hHSD17B13 mice due to the cross-reactivity of antibody. Human HSD17B13 targeted nucleic acid drugs (synthesized according to patents) were efficacious in B-hHSD17B13 mice.

Gene targeting strategy for B-hHSD17B13 mice. The exons 1-7 of mouse Hsd17b13 gene that encode the whole molecule were replaced by human counterparts in B-hHSD17B13 mice. The promoter, 5’UTR and 3’UTR region of the mouse gene are replaced by human counterparts.

Strain specific HSD17B13 expression analysis in wild-type C57BL/6 mice and homozygous humanized B-hHSD17B13 mice by WB. Lung，kidney, liver, stomach, brain, and testis were collected from wild-type C57BL/6 mice (+/+) and homozygous B-hHSD17B13 mice (H/H), and analyzed by western blot (Anti-HSD17B13 antibody: Abcam, ab122036). HSD17B13 was detectable in kidney, liver and stomach of wild-type C57BL/6 mice and homozygous B-hHSD17B13 mice due to the cross-reactivity of antibody.