Basic Information

Strain name
C57BL/6-Hsd17b13tm1(HSD17B13)Bcgen/Bcgen
Common name
B-hHSD17B13 mice
Background
C57BL/6
Catalog number
112658
Aliases
FLDP, HMFN0376, NIIL497, SCDR9, SDR16C3
NCBI gene ID
345275

Description

  • 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.

Targeting strategy

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.

mRNA expression analysis in liver

Species specific analysis of HSD17B13 gene expression in wild-type C57BL/6 mice and homozygous humanized B-hHSD17B13 mice by RT-PCR. Livers were collected from wild-type C57BL/6 mice (+/+) and homozygous B-hHSD17B13 mice (H/H). Mouse Hsd17b13 mRNA was detectable only in wild-type C57BL/6 mice. Human HSD17B13 mRNA was detectable only in homozygous B-hHSD17B13 mice, but not in wild-type C57BL/6 mice.

Species specific analysis of HSD17B13 gene expression in wild-type C57BL/6 mice and heterozygous humanized B-hHSD17B13 mice by RT-qPCR. Livers were collected from wild-type C57BL/6 mice (+/+) and heterozygous B-hHSD17B13 mice (H/+) (n=3). Human HSD17B13 mRNA was detectable only in heterozygous B-hHSD17B13 mice, but not in wild-type C57BL/6 mice. Values are expressed as mean ± SEM.

Protein expression analysis

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.

Inhibitory efficiency of the HSD17B13 targeted nucleic acid drugs

The inhibitory efficiency of the nucleic acid drugs against human HSD17B13 mRNA in liver tissue in homozygous B-hHSD17B13 mice. B-hHSD17B13 mice were randomly divided into two groups (8 weeks old). The human HSD17B13 targeted nucleic acid drugs (synthesized according to patents) and PBS were administered to the mice individually. The nucleic acid drugs were administered in the form of PBS aqueous solution. The mice were sacrificed on day 7, and the liver tissue was collected to detect the expression level of human HSD17B13 mRNA by qPCR. (A) The schematic diagram of experimental processing. (B) The expression of human HSD17B13 mRNA in liver after treatment. The inhibition rate in the treatment group was 75%. The human HSD17B13 in the treatment group (G2) was reduced compared to the control group (G1), demonstrating that B-hHSD17B13 mice provide a powerful preclinical model for in vivo evaluation of human HSD17B13 targeted nucleic acid drugs. Values are expressed as mean ± SEM.

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