More MS news articles for Nov 2001

Chimeric Gene Product Protects Axons From Degeneration

WESTPORT, CT (Reuters Health) Nov 19 - A newly identified chimeric gene slows the degeneration of injured axons in mice, investigators report in the advance online publication of Nature Neuroscience for November 19.

A multinational team led by Dr. Michael P. Coleman, of the University of Cologne in Germany, identified the protective gene, which encodes a fragment of ubiquitination factor E4B (Ube4b) fused to nicotinamide mononucleotide adenylyltransferase (Nmnat), a key enzyme in the synthetic pathway of NAD+.

The investigators generated three lines of transgenic mice expressing the Ube4b/Nmnat gene. The mice with the highest transgene expression level fully preserved transected axons, similar to results in mutant Wld-s mice, which exhibited fully preserved cytoskeleton after 5 days. Wallerian degeneration of injured axons is known to be slowed in Wld-s mutant mice, and the Wld region on mouse chromosome 4 was the site where the Ube4b/Nmnat gene was identified.

The two transgenic lines with lower levels of the transgene showed partially protected axons, while wild-type axons showed clear signs of degeneration.

Even 14 days after transection, axons were protected nearly equivalently in the mice with the highest transgene level and the Wld-s mice, 69% to 73% and 73% to 78%, respectively. "It follows that if Wld protein expression could be raised still further, an even stronger protective effect than in Wld-s and the [high transgene] mice could be achieved," the investigators suggest.

In vitro, the researchers also observed conduction of action potentials and synaptic transmission at neuromuscular junctions, persisting for at least 3 days, in transgenic and Wld-s mutant mouse muscle, but not in wild-type muscle. Transgenic mouse nerve terminals also recycled synaptic vesicles. Both findings suggest that the affected axons were "functionally as well as structurally preserved," Dr. Coleman's team writes.

It is as yet unknown whether Ube4b sequences, Nmnat sequences, or both are required for axon protection. Regardless, identification of the chimeric gene will facilitate studies regarding its protective effects in clinically relevant situations, such as multiple sclerosis, diabetic neuropathy, familial Parkinsonism and spinal cord injury, Dr. Coleman and his colleagues predict.

Nat Neurosci. November 19, 2001. DOI:10.1038/nn770 []

Copyright © 2001 Reuters Ltd