Brainstem axonal degeneration in mice with deletion of selenoprotein p.

Abstract:

:Selenoprotein P is an abundant extracellular protein that is expressed in liver, brain, and other tissues. Studies in mice with the selenoprotein P gene deleted (Sepp-/- mice) have implicated the protein in maintaining brain selenium. Sepp-/- mice fed a normal or low selenium diet develop severe motor impairment and die, but Sepp-/- mice fed a high selenium diet remain clinically unimpaired. As an initial step to evaluate the effect of selenoprotein P deletion on central nervous system architecture, the brains and cervical spinal cords of Sepp-/- and Sepp+/+ mice fed low or high selenium diets were examined by light and electron microscopy. Brains of Sepp-/- mice demonstrated no gross abnormalities. At the light microscopic level, however, Sepp-/- mice fed either the selenium deficient diet or the high selenium diet had enlarged dystrophic axons and degenerated axons in their brainstems and cervical spinal cords. No axonal lesions were observed in the Sepp+/+ mice fed either diet. Electron microscopy demonstrated that the enlarged axons in the Sepp-/- mice were packed with organelles, suggesting a deficit in fast axonal transport. The similar severity of axonal lesions observed in Sepp-/- mice fed the 2 diets suggests that axonal dystrophy is a common phenotype for deletion of selenoprotein P regardless of selenium intake and that additional studies will be required to determine the pathogenesis of the neurological signs and mortality observed in Sepp-/- mice fed a low selenium diet.

journal_name

Toxicol Pathol

journal_title

Toxicologic pathology

authors

Valentine WM,Hill KE,Austin LM,Valentine HL,Goldowitz D,Burk RF

doi

10.1080/01926230500243045

subject

Has Abstract

pub_date

2005-01-01 00:00:00

pages

570-6

issue

5

eissn

0192-6233

issn

1533-1601

pii

VK5307682H745882

journal_volume

33

pub_type

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