Standardized experiments in mutant mice reveal behavioural similarity on 129S5 and C57BL/6J backgrounds.
Genes Brain Behav
; 16(4): 409-418, 2017 04.
Article
em En
| MEDLINE
| ID: mdl-27886459
ABSTRACT
Behavioural analysis of mice carrying engineered mutations is widely used to identify roles of specific genes in components of the mammalian behavioural repertoire. The reproducibility and robustness of phenotypic measures has become a concern that undermines the use of mouse genetic models for translational studies. Contributing factors include low individual study power, non-standardized behavioural testing, failure to address confounds and differences in genetic background of mutant mice. We have examined the importance of these factors using a statistically robust approach applied to behavioural data obtained from three mouse mutations on 129S5 and C57BL/6J backgrounds generated in a standardized battery of five behavioural assays. The largest confounding effect was sampling variation, which partially masked the genetic background effect. Our observations suggest that strong interaction of mutation with genetic background in mice in innate and learned behaviours is not necessarily to be expected. We found composite measures of innate and learned behaviour were similarly impacted by mutations across backgrounds. We determined that, for frequently used group sizes, a single retest of a significant result conforming to the commonly used P < 0.05 threshold results in a reproducibility of 60% between identical experiments. Reproducibility was reduced in the presence of strain differences. We also identified a P-value threshold that maximized reproducibility of mutant phenotypes across strains. This study illustrates the value of standardized approaches for quantitative assessment of behavioural phenotypes and highlights approaches that may improve the translational value of mouse behavioural studies.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Comportamento Animal
/
Mutação
Tipo de estudo:
Prognostic_studies
Limite:
Animals
Idioma:
En
Revista:
Genes Brain Behav
Assunto da revista:
CIENCIAS DO COMPORTAMENTO
/
GENETICA
Ano de publicação:
2017
Tipo de documento:
Article
País de afiliação:
Reino Unido