Out-licensing

A New Mouse Strain with Early Onset of Persistent and Severe Diabetes Mellitus

The new Hnf-1a mutant mice were not created by a simple gene knockout approach that had caused liver dysfunction, severely affected growth and health of the mice and consequently reduced the value of the mice for use in medical research for drug screening and diabetes complication study. Instead, the new Hnf-1a mutant mice were created by the combination of gene knockout, knockin and transgenic approach to modify the mouse Hnf-1a gene alleles, so the Hnf-1a gene alleles were inactivated in the cells of whole body to elicit lifelong diabetes disease, but later reactivated specifically in liver to maintain liver function to ensure the normal growth of the mice. As a result, the new Hnf-1a mutant mice grew normally but at the same time developed severe diabetes. Most importantly, those sicknesses, such as hypertension and kidney disease, developed in the late stage of the mutant mice are largely diabetes-related and can be used in developing therapeutic strategies and in accessing the effects of treatment.

Conclusion

We have used the gene manipulation technologies that include knockout, knockin and transgenic systems to alter the Hnf-1a gene locus in mice, so the Hnf-1a gene is inactivated in the whole body but is later activated only in liver. This is to create a new mouse strain that has normal growth and liver function in early developmental stages but has an early onset of persistent and severe diabetes.

Relevance/Opportunity

This new mouse strain can be used for screening drugs that can enhance insulin production and/or secretion or drugs that can prevent or treat diabetic complications that include hypertension, arthritis, retinal and kidney disorder. Please enquire quoting reference no. 13T-920116 if you are interested in forming licensing or codevelopment partnerships.

Preclinical