Development and Characterization of the SLC46A3 Knockout Mouse Line Summary (1024-character limit) The National Cancer Institute (NCI) seeks licensees for an SLC46A3 knockout mouse line. SLC46A3 is a solute carrier of the Major Facilitator Superfamily (MFS) and is thought to have roles in multiple diseases including nonalcoholic fatty disease, liver cancer and .

NIH Reference Number E-152-2021

Product Type Research Tools

Keywords SLC46A3, , Major Facilitator Superfamily, MFS, Nonalcoholic fatty liver disease, Obesity, Liver Cancer, , Knockout Mouse, 2,3,7,8-tetracholodibenzo-p- dioxin, TCDD, Gonzalez

Collaboration Opportunity This invention is available for licensing.

Contact Michael Salgaller, Ph.D. NCI - National Cancer Institute

240-276-5476

[email protected]

Description of Technology

Nonalcoholic fatty liver disease is caused by several factors including 2,3,7,8-tetrachlorodibenzo-p- dioxin (TCDD), an environmental contaminant. TCDD causes lipid accumulation in by inducing the Solute Carrier Family 46 Member 3 (SLC46A3) expression. To effectively study TCDD- mediated lipid accumulation, research tools such as SLC46A3 knockout cells and animal models are required.

Researchers at the National Cancer Institute (NCI) have developed an SLC46A3 knockout mouse line and demonstrated that TCDD-induced hepatic accumulation was significantly reduced in the knockout mice compared to the wild type mice. This reduction in triglyceride accumulation was more pronounced when the mice were fed a high fat diet. The SLC46A3 knockout mouse line is therefore an effective tool to study TCDD-induced lipid accumulation, liver toxicity and nonalcoholic fatty liver

NCI Technology Transfer Center https://techtransfer.cancer.gov/pdf/e-152-2021.pd f disease. As SLC46A3 gene and are also associated with other diseases such as , , liver cancer, papilloma, , obesity, and SARS, this knockout mouse line may have wide applicability.

The NCI is seeking licensees for the SLC46A3 knockout mouse line.

Potential Commercial Applications Drug screening and development against various diseases such as nonalcoholic fatty liver disease, obesity, liver cancer, SARS, breast cancer, prostate cancer, papilloma, glioma Research tool to study SLC46A3’s role in hepatic lipid accumulation or as a solute carrier of the Major Facilitator Superfamily (MFS)

Competitive Advantages The only known SLC46A knockout mouse line available Effective research tool to study TCDD-mediated liver toxicity leading to nonalcoholic fatty liver disease

Inventor(s)

Frank J Gonzalez Ph.D. (NCI), Sun Hee Yim Ph.D, Jung-Hwan Kim Ph.D

Development Stage Pre-clinical (in vivo)

Publications

Kim JH, et al. Lysosomal SLC46A3 modulates hepatic cytosolic copper

Patent Status Research Material: NIH will not pursue patent prosecution for this technology

Therapeutic Area Cancer/Neoplasm Hormonal Systems, Endocrine, and Metabolic Diseases

NCI Technology Transfer Center https://techtransfer.cancer.gov/pdf/e-152-2021.pd f