Application
Pre-clinical rodent model to study classic galactosemia disease.
Key Benefits
- Identify striking differences in GALT-independent galactose metabolism among tissues and across post-natal time points.
- Study the relationship between galactose metabolite levels in blood and other tissues.
- Study the impact of rigorous galactose restriction diet.
- Identify biomarkers for classic galactosemia.
Market Summary
Classic galactosemia (CG) is a potentially lethal inborn error of galactose metabolism. Although newborn screening and rapid dietary restriction of galactose can prevent or resolve the potentially lethal acute symptoms of CG, most treated patients experience significant complications such as cognitive impairment, speech difficulties, neuromuscular problems, and premature ovarian insufficiency, among others by mid-childhood. The mechanisms underlying these long-term deficits remain unclear mostly due to the lack of appropriate animal models.
Technical Summary
Researchers at Emory University have created a GALT-null Sprague-Dawley outbred rat using CRISPR-Cas9 technology to serve as a model for classic galactosemia (CG). This is the first GALT-null mammalian model reported to show cognitive deficits and can be used to explore the relationship between galactose metabolites and different outcomes. The GALT-null rat exhibits a range of phenotypes reminiscent of CG in humans, including cataracts, mild growth delay, and both cognitive impairment and motor deficits in adults. This model offers first clues to the tissue-specific and longitudinal consequences of GALT deficiency in mammals and set the stage for future studies of mechanism and intervention in CG.
Development Stage
Creation and characterization of in vivo rodent model.
Publication
Daenzer, J. M., Rasmussen, S. A., Patel, S., McKenna III, J., & Fridovich‐Keil, J. L. (2022). Neonatal GALT gene replacement offers metabolic and phenotypic correction through early adulthood in a rat model of classic galactosemia. Journal of inherited metabolic disease, 45(2), 203-214.
