Spontaneous Spongiform Brainstem Degeneration in a Young Mouse Lemur (Microcebus murinus) with Conspicuous Behavioral, Motor, Growth, and Ocular Pathologies

Abstract

The nocturnal and omnivorous mouse lemurs are the world's smallest primates. Therefore, they can efficiently be maintained and bred. 12,45 Mouse lemurs show high species diversity, with at least 24 phylogenetically distinct species which have unique and disparate ranges in the remaining tropical primary and secondary forests of Madagascar. 33 Various studies have shown that one of the phylogenetically defined species, the gray mouse lemur (Microcebus murinus), is a valuable model of age-related neurodegeneration (for a recent review, see reference 39): a significant proportion of aged subjects exhibit progressive cerebral atrophy, 32 whereas others demonstrate accumulations of amyloid plaques and tau protein. 23 Both of these brain morphologic and biochemical abnormalities are seen in human Alzheimer disease and may be linked to cognitive decline in mouse lemurs. 32,39 Standardized, computerized cognitive tasks comparable to the Cambridge Neuropsychological Test Automated Battery used in human diagnostics and research on psychiatric diseases, such as Alzheimer disease and schizophrenia, 2,11 have recently been translated to the mouse lemur NHP model. 21,37 Worldwide, gray mouse lemurs currently are bred in 4 major captive colonies. 12 The mean lifespan in the Hannover colony, where the animal we describe here was born, is 7.7 y. 45 The genome of the gray mouse lemur has recently been sequenced, assembled, and annotated with more than 20,000 protein-coding genes (NCBI genome assembly accession GCF_000165445.2). 24 As a result of these various analyses, mouse lemurs represent a promising NHP model for evolutionary 26,30,36,43,44 and biomedical research. 12,21,25,39 Here, we report a case of spontaneous spongiform brainstem degeneration with associated abnormalities of the cerebrum and ventricles in a young female gray mouse lemur. This animal presented with prominent growth retardation, bilateral early cataracts, and conspicuous behavioral, motor, and brain structural anomalies. Immunohistochemical