GLI-Similar 3(GLIS3) Knock Out (KO) Mice as Models to Screen Therapeutics for Diabetes, Polycystic Kidney Disease, and Hypothyroidism

GLI-similar (Glis) 1-3 proteins constitute a subfamily of the Krüppel-like zinc finger transcription factors that are closely related to the Gli family. Mutations in human GLIS3 have been implicated in a syndrome characterized by neonatal diabetes and congenital hypothyroidism (NDH) and in some patients accompanied by polycystic kidney disease, glaucoma, and liver fibrosis. To further identify and study the physiological functions of GLIS3, NIEHS investigators generated mice in which GLIS3 is ubiquitously knocked out (GLIS3-KO) or conditionally knocked out in a cell type-specific manner. GLIS3-KO mice develop polycystic kidney disease, hypothyroidism, and neonatal diabetes, as indicated by the development of hyperglycemia and hypoinsulinemia. The pancreatic endocrine cells, particularly insulin-producing pancreatic beta cells, are greatly diminished in these mice. The pancreas-selective knockout mice GLIS3(Pdx1-Cre) develop severe diabetes within 2-3 months, much later than the GLIS3-KO mice. The kidney-selective knockout of GLIS3 (GLIS3(Ksp-Cre) mice lack expression of GLIS3 in the collecting ducts and develop severe polycystic kidney disease within a period of 2-4 months. These mice can be used as models to screen therapeutics for diabetes, polycystic kidney disease, and hypothyroidism.

Potential Commercial Applications: Competitive Advantages:
  • Therapeutic target in the management of diabetes, polycystic kidney disease, and hypothyroidism
  • Models to test therapeutic drugs for diabetes, polycystic kidney disease, and hypothyroidism
  • Provides opportunity to discover upstream signals that regulate GLIS3 activity
  • Can be used in stem cell therapy in diabetes treatment
  • Excellent model to study the role of GLIS3 in neonatal diabetes

Development Stage:
  • Early-stage
  • Pre-clinical
  • In vivo data available (animal)

Related Invention(s):


Anton Jetten (NIEHS)  ➽ more inventions...

Hong Soon Kang (NIEHS)  ➽ more inventions...

Kristin Lichti-Kaiser (NIEHS)  ➽ more inventions...

Intellectual Property:
Research Tool — Patent protection is not being pursued for this technology.

Kang HS, et al. PMID 19805515
Kang HS, et al. PMID 19273592

Collaboration Opportunity:

The NIEHS is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate or commercialize GLIS3 Knock Out Mice. For collaboration opportunities, please contact Sharon Soucek, Ph.D. at

Licensing Contact:
Vidita Choudhry, Ph.D.
Phone: 301-594-4095

OTT Reference No: E-303-2011-0
Updated: Sep 4, 2020