Antecedent presentation of neurological phenotypes in the Collaborative Cross reveals four classes with complex sex-dependencies

Antecedent viral infection may contribute to increased susceptibility to several neurological diseases, such as multiple sclerosis and Parkinson’s disease. Variation in clinical presentations of these diseases is often associated with gender, genetic background, or a combination of these and other f...

Full description

Saved in:

Bibliographic Details
Published in:	Scientific reports Vol. 10; no. 1; p. 7918
Main Authors:	Eldridge, Raena, Osorio, Daniel, Amstalden, Katia, Edwards, Caitlin, Young, Colin R., Cai, James J., Konganti, Kranti, Hillhouse, Andrew, Threadgill, David W., Welsh, C. Jane, Brinkmeyer-Langford, Candice
Format:	Journal Article
Language:	English
Published:	London Nature Publishing Group UK 13-05-2020 Nature Publishing Group
Subjects:	631/1647/2198 64/60 692/617/375/1367 Animal models Animals Cluster Analysis Collaboration Crosses, Genetic Disease Encephalitis - etiology Encephalomyelitis Female Gait Gender Genetic Association Studies H-2 Antigens - genetics Humanities and Social Sciences Infections Male Mice Movement disorders multidisciplinary Multiple sclerosis Neurodegenerative diseases Neurological diseases Paralysis Paresis Parkinson's disease Phenotype Phenotypes Phenotyping Poliomyelitis - etiology Rodents Science Science (multidisciplinary) Seizures Seizures - etiology Sex Sex Factors Species Specificity Strains (organisms) Theilovirus - physiology Viral infections Viral Load
Online Access:	Get full text
Tags:	Add Tag No Tags, Be the first to tag this record!

Description
Summary:	Antecedent viral infection may contribute to increased susceptibility to several neurological diseases, such as multiple sclerosis and Parkinson’s disease. Variation in clinical presentations of these diseases is often associated with gender, genetic background, or a combination of these and other factors. The complicated etiologies of these virally influenced diseases are difficult to study in conventional laboratory mouse models, which display a very limited number of phenotypes. We have used the genetically and phenotypically diverse Collaborative Cross mouse panel to examine complex neurological phenotypes after viral infection. Female and male mice from 18 CC strains were evaluated using a multifaceted phenotyping pipeline to define their unique disease profiles following infection with Theiler’s Murine Encephalomyelitis Virus, a neurotropic virus. We identified 4 distinct disease progression profiles based on limb-specific paresis and paralysis, tremors and seizures, and other clinical signs, along with separate gait profiles. We found that mice of the same strain had more similar profiles compared to those of different strains, and also identified strains and phenotypic parameters in which sex played a significant role in profile differences. These results demonstrate the value of using CC mice for studying complex disease subtypes influenced by sex and genetic background. Our findings will be useful for developing novel mouse models of virally induced neurological diseases with heterogenous presentation, an important step for designing personalized, precise treatments.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	2045-2322 2045-2322
DOI:	10.1038/s41598-020-64862-z