Technology ID
TAB-3614

Mmut p.G715v/p.G71 Knock-ln Methylmalonyl-CoA Mutase (Mmut) Allele Mouse Models for the Study of Methylmalonic Acidemia (MMA)

E-Numbers
E-160-2020-0
Lead Inventor
Venditti, Charles (NHGRI)
Co-Inventors
Schneller, Jessica (NHGRI)
Chandler, Randy (NHGRI)
Applications
Therapeutics
Research Materials
Therapeutic Areas
Ophthalmology
Oncology
Infectious Disease
Endocrinology
Dental
Cardiology
Lead IC
NHGRI
ICs
NHGRI
Isolated Methylmalonic Acidemia (MMA) comprises a relatively common and heterogeneous group of inborn errors of metabolism. In order to create mouse models of MMA to resemble the pathogenic mutations seen in patients, the NHGRI scientist used genome editing to generate new mutants of Mmut allele -p.G715V. This allele recapitulates a missense mutation seen in multiple patients with the disorder. Of note and emphasis is the fact that there are no transgene cassettes or other alternations to the Mmut locus in these new mouse models. These mice display elevations of MMA biomarkers, such as 2-methylcitrate, are viable, without obvious gross pathology, and fully fertile, they can be easily bred. These new models can be used for physiology studies, biomarker discovery, and to test the effects of gene therapy, cell therapy, mRNA therapy, nucleic acid therapies, small molecules, the microbiome, and especially genome editing using AAV, Cas/CRISPR, and other editing approaches as treatments for MMA and related conditions.
Commercial Applications
These new models can be used for physiology studies, biomarker discovery, and to test the effects of gene therapy, cell therapy, mRNA therapy, nucleic acid therapies, small molecules, the microbiome, and especially genome editing using adeno-associated viruses (AAV), Cas/CRISPR, and other editing approaches as treatments for MMA and related conditions.

Competitive Advantages
The Mmut 6115v/G7isv mice are especially unique in that they are viable, can be bred in larger quantities than other mouse models, display modest biochemical changes associated with MMA and can be induced to be very sick by a simple manipulation of dietary change. They also have MMA related disease processes in all the tissues and cells of the body. Furthermore, we have demonstrated the utility of these mice to test AAV gene therapy as a therapeutic intervention.
Licensing Contact:
Campbell, Eggerton
eggerton.campbell@nih.gov