Abstract
BXD recombinant inbred (RI) lines represent a genetic reference population derived from a cross between C57BL/6J mice (B6) and DBA/2J mice (D2), which through meiotic recombination events possesses recombinant chromosomes containing B6 or D2 haplotype segments. The quantitative trait loci (QTLs) are the locations of segregating genetic polymorphisms and are fundamental to understanding genetic diversity in human disease susceptibility and severity. QTL mapping represents the typical approach for identifying naturally occurring polymorphisms that influence complex phenotypes. In this process, genotypic values at markers of known genomic locations are associated with phenotypic values measured in a segregating population. Indeed, BXD RI strains provide a powerful tool to study neurotoxicity induced by different substances. In this review, we describe the use of BXD RI lines to understand the underlying mechanisms of neurotoxicity in response to ethanol and cocaine, as well as metals and pesticide exposures.
Highlights
The development of an optimal experimental design requires the selection of an adequate animal model
The BXD recombinant inbred (RI) lines represent a genetic reference population derived from a cross between C57BL/6J mice and DBA/2J mice using a strategy of advanced intercrosses [1,2]
The BXD RI murine family consists of approximately 150 strains with greater than 6 million sequence variants, a level similar to the human cohorts that are being studied in genome-wide association studies (GWASs)
Summary
The development of an optimal experimental design requires the selection of an adequate animal model. The BXD RI model has been considered adequate for the analysis of the genetic variability in the context of human disease etiology [1,3] As these strains are inbred, the same genome can be studied repeatedly, providing an optimal model to investigate disease models [4]. The relevance of the BXD RI family has been extended to the analysis of the genetics of behavioral phenotypes, including alcohol and drug addiction [8,9,10,11,12,13,14], neurodegenerative processes [4,6,15,16,17], heavy metals and pesticides [3,18,19], and changes related to the degeneration of the visual system [20,21,22]. We discuss the potential for the BXD RI family to advance the mechanistic understanding of neurotoxicity in response to ethanol and drugs of abuse, as well as metals and pesticide exposures
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