Brain and spinal cord lesions in 28 inbred strains of aging mice.

Document Type

Article

Publication Date

11-1-2022

Publication Title

Veterinary pathology

Keywords

JMG, Aging, Animals, Female, Male, Medulla Oblongata, Mice, Mice, Inbred Strains, Proteasome Endopeptidase Complex, Spinal Cord, Ubiquitins

JAX Source

Vet Pathol. 2022;59(6):1047-55

Volume

59

Issue

6

First Page

1047

Last Page

1055

ISSN

1544-2217

PMID

36062914

DOI

https://doi.org/10.1177/03009858221120009

Grant

The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: This work was supported by grants from the Ellison Medical Foundation, the National Institutes of Health (AG25707), and the American Lebanese Syrian Association (ALSAC).

Abstract

Brain and spinal cord histopathology findings in male and female 20-month-old mice in a large-scale aging study of 28 inbred Jackson Laboratory mouse strains from 7 genetic families are described. Brain sections from selected strains at 12 and 24 months of age or older were also reviewed. Common lesions include axonal dystrophy in the gracile and/or cuneate nucleus in the sensory tract of the dorsal medulla and in the spinal cord in all strains. Hirano-like bodies were seen in 24/28 strains, and mineralization was observed in the thalamus of 9/28 strains. Less common lesions were also seen in the cerebellum, cerebral cortex, and other brain areas. No brain or spinal cord tumors were found. Evidence of an impairment of the ubiquitin-proteasome system (UPS) and/or suspected autophagy was manifested as medullary axonal dystrophy with intra-axonal granular eosinophilic bodies and LC3B immunohistochemistry in most strains. RIIIS/J, the most severely affected strain, showed moderate axonal dystrophy at 12 months, which progressed to severe lesions at 20 months. Comparative pathology in various species is discussed.

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