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

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Here we report a case of severe growth retardation and neurologic abnormalities in a female gray mouse lemur (Microcebus murinus), a small NHP species for which the genomic sequence recently became available. The female lemur we present here died on postnatal day 125. This lemur had impaired development of motor skills and showed severe ataxia and tremors. In addition, hearing seemed normal whereas ophthalmic examination revealed incipient bilateral cataracts, abnormal pigmentation in the lens of the left eye, and a missing optokinetic nystagmus, which indicated impaired vision. Most prominently, the lemur showed severe growth retardation. Necropsy revealed maldevelopment of the left reproductive organs and unilateral dilation of the right lateral ventricle, which was confirmed on brain MRI. Brain histology further revealed large, bilateral areas of vacuolation within the brainstem, but immunohistochemistry indicated no sign of pathologic prion protein deposition. Full genomic sequencing of the lemur revealed a probably pathologic mutation in LARGE2 of the LARGE gene family, which has been associated with congenital muscular dystrophies. However, potentially functional mutations in other genes were also present. The observed behavioral and motor signs in the presented animal might have been linked to spongiform degeneration and resulting brainstem dysfunction and progressive muscle weakness. The macroscopic developmental abnormalities and ophthalmic findings might be genetic in origin and linked to the mutation in LARGE2.
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Document Type: Case Report

Affiliations: 1: Institute of Zoology, University of Veterinary Medicine Hannover, Hannover, Lower Saxony, Germany, Center for Neuroscience Systems Hannover, Hannover, Lower Saxony, Germany;, Email: [email protected] 2: Department of Pathology, University of Veterinary Medicine Hannover, Hannover, Lower Saxony, Germany 3: Institute of Zoology, University of Veterinary Medicine Hannover, Hannover, Lower Saxony, Germany 4: Institute of Zoology, University of Veterinary Medicine Hannover, Hannover, Lower Saxony, Germany, Center for Neuroscience Systems Hannover, Hannover, Lower Saxony, Germany 5: Center for Neuroscience Systems Hannover, Hannover, Lower Saxony, Germany, Department of Pathology, University of Veterinary Medicine Hannover, Hannover, Lower Saxony, Germany 6: Small Animal Clinic, University of Veterinary Medicine Hannover, Hannover, Lower Saxony, Germany 7: Imaging Center, Institute of Laboratory Animal Science, Hannover Medical School, Hannover, Lower Saxony, Germany 8: Institute of Novel and Emerging Infectious Diseases, FriedrichLoeffler-Institute, Federal Research Institute for Animal Health, Greifswald, Mecklenburg Western Pomerania, Germany 9: Department of Molecular and Human Genetics and Human Genome Sequencing Center, Baylor College of Medicine, Houston, Texas

Publication date: December 1, 2018

This article was made available online on November 28, 2018 as a Fast Track article with title: "Spontaneous Spongiform Brainstem Degeneration in a Young Mouse Lemur (Microcebus murinus) with Conspicuous Behavioral, Motor, Growth, and Ocular Pathologies".

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  • Comparative Medicine (CM), an international journal of comparative and experimental medicine, is the leading English-language publication in the field and is ranked by the Science Citation Index in the upper third of all scientific journals. The mission of CM is to disseminate high-quality, peer-reviewed information that expands biomedical knowledge and promotes human and animal health through the study of laboratory animal disease, animal models of disease, and basic biologic mechanisms related to disease in people and animals.

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