Impact of C57BL/6 substrain on sex-dependent differences in mouse stroke models. (July 2019)

• Record Type: Journal Article
• Authors: Nowak, Thaddeus S.; Mulligan, Megan K.
• Is Part Of: Neurochemistry international. Volume 127(2019)
• Page Start: 12
• Page End: 21
• Publication Date: 2019-07
• Subjects: C57BL/6 mouse -- Substrain -- Experimental stroke -- Sex differences; Neurochemistry -- Periodicals; Neurochemistry -- Periodicals; Neurochimie -- Périodiques; Neurochemistry; Periodicals; 612.804205
• DOI: 10.1016/j.neuint.2018.11.011
• Languages: English
• ISSNs: 0197-0186

Abstract

Abstract: We have recently found significant variation in stroke vulnerability among substrains of C57BL/6 mice, observing that commonly used N-lineage substrains exhibit larger infarcts than C57BL/6J and related substrains. Parallel variation was also seen with respect to sex differences in stroke vulnerability, in that C57BL/6 mice of the N-lineage exhibited comparable infarct sizes in males and females, whereas infarcts tended to be smaller in females than in males of J-lineage substrains. This adds to the growing list of recognized phenotypic and genetic differences among C57BL/6 substrains. Although no previous studies have explicitly compared substrains with respect to sex differences in stroke vulnerability, unrecognized background mismatch has occurred in some studies involving control and genetically modified mice. The aims of this review are to: present the evidence for associated substrain- and sex-dependent differences in a mouse permanent occlusion stroke model; examine the extent to which the published literature in other models compares with these recent results; and consider the potential impact of unrecognized heterogeneity in substrain background on the interpretation of studies investigating the impact of genetic modifications on sex differences in stroke outcome. Substrain emerges as a critical variable to be documented in any experimental stroke study in mice. Highlights: C57BL/6 mouse substrains differ in stroke vulnerability. Sex differences in stroke outcome are also dependent on substrain background. Background mismatch can confound studies involving genetically modified strains. C57BL/6 substrain is a critical variable to document in experimental stroke.