Stathmin-deficient mice develop an age-dependent axonopathy of the central and peripheral nervous systems.
Stathmin is a cytosolic protein that binds tubulin and destabilizes cellular microtubules, an activity regulated by phosphorylation. Despite its abundant expression in the developing mammalian nervous system and despite its high degree of evolutionary conservation, stathmin-deficient mice do not exhibit a developmental phenotype.(1) Here we report that aging stathmin(-/-) mice develop an axonopathy of the central and peripheral nervous systems. The pathological hallmark of the early axonal lesions was a highly irregular axoplasm predominantly affecting large, heavily myelinated axons in motor tracts. As the lesions progressed, degeneration of axons, dysmyelination, and an unusual glial reaction were observed. At the functional level, electrophysiology recordings demonstrated a significant reduction of motor nerve conduction velocity in stathmin(-/-) mice. At the molecular level, increased gene expression of SCG 10-like protein, a stathmin-related gene with microtubule destabilizing activity, was detected in the central nervous system of aging stathmin(-/-) mice. Together, these findings suggest that stathmin plays an essential role in the maintenance of axonal integrity.
Liedtke
Wolfgang
W
Department of Pathology, Albert Einstein College of Medicine, Bronx, New York. wolfgang.liedtke@mail.rockefeller.edu
Leman
Elizabeth E
EE
Fyffe
Robert E W
RE
Raine
Cedric S
CS
Schubart
Ulrich K
UK
D000375:Aging; D000818:Animals; D001369:Axons / Q000648:ultrastructure*; D002135:Calcium-Binding Proteins; D002352:Carrier Proteins; D002490:Central Nervous System / Q000473:pathology* / Q000503:physiopathology; D002874:Chromosome Mapping; D002878:Chromosomes, Human, Pair 1; D005786:Gene Expression Regulation; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D051379:Mice; D018345:Mice, Knockout; D008868:Microtubule Proteins; D009414:Nerve Growth Factors / Q000235:genetics / Q000378:metabolism; D009422:Nervous System Diseases / Q000473:pathology* / Q000503:physiopathology; D009431:Neural Conduction / Q000502:physiology; D017933:Peripheral Nervous System / Q000473:pathology* / Q000503:physiopathology; D010641:Phenotype; D010750:Phosphoproteins / Q000235:genetics / Q000502:physiology*; D011897:Random Allocation; D012160:Retina / Q000378:metabolism / Q000473:pathology; D013116:Spinal Cord / Q000378:metabolism; D050777:Stathmin
D002135:Calcium-Binding Proteins; D002352:Carrier Proteins; D005904:Glial Fibrillary Acidic Protein; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D008868:Microtubule Proteins; D009414:Nerve Growth Factors; D010750:Phosphoproteins; C493995:STMN1 protein, human; C063314:STMN2 protein, human; C112285:STMN3 protein, human; C491795:STMN4 protein, human; D050777:Stathmin; C493994:Stmn1 protein, mouse; C512849:Stmn2 protein, mouse; C512848:Stmn2 protein, rat; C491793:Stmn3 protein, mouse; C491792:Stmn3 protein, rat; C491794:Stmn4 protein, mouse