Spontaneous Murine Neuroaxonal Dystrophy: a Model of Infantile Neuroaxonal Dystrophy

D. M. Bouley; J. J. McIntire; B. T. Harris; R. J. Tolwani; G. M. Otto; R. H. DeKruyff; S. J. Hayflick

doi:10.1016/j.jcpa.2005.10.002

Spontaneous Murine Neuroaxonal Dystrophy: a Model of Infantile Neuroaxonal Dystrophy

D. M. Bouley, J. J. McIntire, B. T. Harris, R. J. Tolwani, G. M. Otto, R. H. DeKruyff, S. J. Hayflick

Molecular and Medical Genetics

Research output: Contribution to journal › Article › peer-review

14 Scopus citations

Abstract

The neuroaxonal dystrophies (NADs) in human beings are fatal, inherited, neurodegenerative diseases with distinctive pathological features. This report describes a new mouse model of NAD that was identified as a spontaneous mutation in a BALB/c congenic mouse strain. The affected animals developed clinical signs of a sensory axonopathy consisting of hindlimb spasticity and ataxia as early as 3 weeks of age, with progression to paraparesis and severe morbidity by 6 months of age. Hallmark histological lesions consisted of spheroids (swollen axons), in the grey and white matter of the midbrain, brain stem, and all levels of the spinal cord. Ultrastructural analysis of the spheroids revealed accumulations of layered stacks of membranes and tubulovesicular elements, strongly resembling the ultrastructural changes seen in the axons of human patients with endogenous forms of NAD. Mouse NAD would therefore seem a potentially valuable model of human NADs.

Original language	English (US)
Pages (from-to)	161-170
Number of pages	10
Journal	Journal of Comparative Pathology
Volume	134
Issue number	2-3
DOIs	https://doi.org/10.1016/j.jcpa.2005.10.002
State	Published - Feb 2006

Keywords

man
mouse model
neuroaxonal dystrophy
spheroids

ASJC Scopus subject areas

Pathology and Forensic Medicine
General Veterinary

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10.1016/j.jcpa.2005.10.002

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title = "Spontaneous Murine Neuroaxonal Dystrophy: a Model of Infantile Neuroaxonal Dystrophy",

abstract = "The neuroaxonal dystrophies (NADs) in human beings are fatal, inherited, neurodegenerative diseases with distinctive pathological features. This report describes a new mouse model of NAD that was identified as a spontaneous mutation in a BALB/c congenic mouse strain. The affected animals developed clinical signs of a sensory axonopathy consisting of hindlimb spasticity and ataxia as early as 3 weeks of age, with progression to paraparesis and severe morbidity by 6 months of age. Hallmark histological lesions consisted of spheroids (swollen axons), in the grey and white matter of the midbrain, brain stem, and all levels of the spinal cord. Ultrastructural analysis of the spheroids revealed accumulations of layered stacks of membranes and tubulovesicular elements, strongly resembling the ultrastructural changes seen in the axons of human patients with endogenous forms of NAD. Mouse NAD would therefore seem a potentially valuable model of human NADs.",

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author = "Bouley, {D. M.} and McIntire, {J. J.} and Harris, {B. T.} and Tolwani, {R. J.} and Otto, {G. M.} and DeKruyff, {R. H.} and Hayflick, {S. J.}",

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AU - Bouley, D. M.

AU - McIntire, J. J.

AU - Harris, B. T.

AU - Tolwani, R. J.

AU - Otto, G. M.

AU - DeKruyff, R. H.

AU - Hayflick, S. J.

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N2 - The neuroaxonal dystrophies (NADs) in human beings are fatal, inherited, neurodegenerative diseases with distinctive pathological features. This report describes a new mouse model of NAD that was identified as a spontaneous mutation in a BALB/c congenic mouse strain. The affected animals developed clinical signs of a sensory axonopathy consisting of hindlimb spasticity and ataxia as early as 3 weeks of age, with progression to paraparesis and severe morbidity by 6 months of age. Hallmark histological lesions consisted of spheroids (swollen axons), in the grey and white matter of the midbrain, brain stem, and all levels of the spinal cord. Ultrastructural analysis of the spheroids revealed accumulations of layered stacks of membranes and tubulovesicular elements, strongly resembling the ultrastructural changes seen in the axons of human patients with endogenous forms of NAD. Mouse NAD would therefore seem a potentially valuable model of human NADs.

AB - The neuroaxonal dystrophies (NADs) in human beings are fatal, inherited, neurodegenerative diseases with distinctive pathological features. This report describes a new mouse model of NAD that was identified as a spontaneous mutation in a BALB/c congenic mouse strain. The affected animals developed clinical signs of a sensory axonopathy consisting of hindlimb spasticity and ataxia as early as 3 weeks of age, with progression to paraparesis and severe morbidity by 6 months of age. Hallmark histological lesions consisted of spheroids (swollen axons), in the grey and white matter of the midbrain, brain stem, and all levels of the spinal cord. Ultrastructural analysis of the spheroids revealed accumulations of layered stacks of membranes and tubulovesicular elements, strongly resembling the ultrastructural changes seen in the axons of human patients with endogenous forms of NAD. Mouse NAD would therefore seem a potentially valuable model of human NADs.

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Spontaneous Murine Neuroaxonal Dystrophy: a Model of Infantile Neuroaxonal Dystrophy

Abstract

Keywords

ASJC Scopus subject areas

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