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The article discusses research of Ebola hemorrhagic fever pathogenesis and resistance using mouse models. The authors note that a mouse-adapted strain of Ebola virus (MA-EBOV) does not reproduce the hallmark symptoms of Ebola virus disease, thus limiting pathogenesis studies to nonhuman primates. The disease phenotypes exhibited by recombinant inbred mice after mouse-adapted Ebola virus infection that suggests susceptibility to Ebola hemorrhagic fever is genetically based are discussed.

The inbred mouse C57BL/6J is the reference strain for genome sequence and for most behavioral and physiological phenotypes. However, the International Knockout Mouse Consortium uses an embryonic stem cell line derived from a related C57BL/6N substrain. We found that C57BL/6N has a lower acute and sensitized response to cocaine and methamphetamine. We mapped a single causative locus and identified a nonsynonymous mutation of serine to phenylalanine (S968F) in Cytoplasmic FMRP interacting protein 2 (Cyfip2) as the causative variant. The S968F mutation destabilizes CYFIP2, and deletion of the C57BL/6N mutant allele leads to acute and sensitized cocaine-response phenotypes. We propose that CYFIP2 is a key regulator of cocaine response in mammals and present a framework to use mouse substrains to identify previously unknown genes and alleles regulating behavior. [ABSTRACT FROM AUTHOR]