Mouse model of retinitis pigmentosa shows key biochemical, diagnostic features of human disease

Retinitis pigmentosa (RP) is a group of rare, genetic disorders that involve a breakdown and loss of cells in the retina. Retinal degeneration in RP is caused by a family of hereditary mutations that slowly lead to blindness over years or decades. One of these forms of RP, called RP59, is caused by the mutation of one amino acid in an enzyme called DHDDS that is part of an enzyme complex involved in the glycosylation of proteins. (Glycosylation is the process by which sugar ‘trees’ are created, altered and attached to 1000’s of proteins or fats. Amino acids are the building blocks of proteins.)  The K42E mouse model of RP59, first reported in 2020 by Steven Pittler, Ph.D. and colleagues at the University of Alabama at Birmingham and elsewhere, replicates this mutation by changing the same amino acid in the mouse enzyme. 

A preliminary study of the K42E mouse model showed lack of profound retinal degeneration and protein glycosylation defects. However, a new study published in the journal Cell Death and Disease shows that the model exhibits key biochemical and diagnostic features of human RP59. “Further, we show structural and inner retina functional deficits in the K42E mouse model…,” said Pittler. “This investigation may provide novel insights into RP59 disease mechanism that will guide future testing of therapeutic interventions to slow or halt the progression of this blinding disorder.”

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Medical Xpress, October 31, 2023; see source article Mai N. Nguyen et al, Cell Death & Disease (2023). DOI: 10.1038/s41419-023-05936-4