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

• Published in: Veterinary pathology Vol. 59; no. 6; pp. 1047 - 1055
• Main Authors: Ward, Jerrold M., Vogel, Peter, Sundberg, John P.
• Format: Journal Article
• Language: English
• Published: Los Angeles, CA SAGE Publications 01.11.2022
• Subjects: Aging; Animals; Female; Male; Medulla Oblongata - pathology; Mice; Mice, Inbred Strains; Proteasome Endopeptidase Complex; Spinal Cord - pathology; Ubiquitins; mouse; autophagy; gracile nucleus; cuneate nucleus; Hirano-like bodies; aging; spheroids; axonal dystrophy; neuropathology
• ISSN: 0300-9858; 1544-2217
• DOI: 10.1177/03009858221120009

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.