The loss of neurons associated with such diseases as Alzheimer's and Parkinson's have long been attributed to neural degeneration. But could this degeneration actually belie underlying problems in regeneration? Jian Zuo, St. Jude Children's Research Hospital, Memphis, Tennessee, and coworkers elsewhere, report in today's Science that there is a direct link between Purkinje cell degeneration and the Nna1 gene, which is induced during axonal regeneration.

The authors found that mutations in the Nna1 gene are responsible for mice with the Purkinje cell degeneration (pcd) phenotype. These mice behave normally until adolescence, whereupon Purkinje cells and cells of the thalamus begin to degenerate. The first hints at the role of Nna1 came from mapping experiments, which placed the pcd mutations in a 600 kb region of chromosome thirteen harboring Nna1. But the clincher was finding that this gene is barely expressed in three independent pcd mouse lines (pcd1J - pcd3J). Zuo et al. subsequently found a transposable element in intron 13 of pcd2J, while in pcd3J they found a 12kb deletion between exons five and eight. The authors failed to find any mutations in the Nna1 coding sequence of the pcd1J strain, suggesting there may be mutations lurking in the regulatory region of that gene.

The exact function of Nna1 is not known. It is induced when axons of spinal neurons are severed and is expressed throughout the brain. The gene is also expressed in the testis and photoreceptors of the retina, which explains why pcd mice are infertile and have progressively deteriorating vision.—Tom Fagan

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Primary Papers

  1. . Purkinje cell degeneration (pcd) phenotypes caused by mutations in the axotomy-induced gene, Nna1. Science. 2002 Mar 8;295(5561):1904-6. PubMed.