Supplementary MaterialsTable 01. NL3R451C mutant mice on a 100 % pure C57BL6J background didn’t display spatial storage enhancements or public conversation deficits. We just observed a reduce startle response and mildly elevated locomotor activity in these mice suggesting that history genetics influences behavioral outcomes relating to the NL3R451C mutation. and genes have already been implicated in autism and intellectual disability (Jamain et al., 2003; Cao and Tabuchi, 2016). Early autism genetic research determined a missense Linagliptin biological activity mutation in leading to an arginine to cysteine substitution at conserved amino acid placement 451 in two brothers, one with serious autism and one with Aspergers syndrome, a milder form of autism (Jamain et al., 2003). Heterogeneity involving the same genetic mutation raises an interesting question as to what may influence behavioral variations in two brothers with the same NL3R451C mutation. One explanation for phenotypic variability involving the same mutation is definitely genetic heterogeneity (Hummel et al., 1972; Threadgill et al., 1995; Crawley, 1996; Gerlai, 1996). While the mutation may be the same, the variations in a number of additional genes can play a role in phenotypic variation. Phenotypic variation has also been observed in mouse models involving the gene mutation NL3R451C. Initial behavioral studies of mice harboring a NL3R451C ENG mutation on a hybrid C57BL6J/129S2/SvPasCrl genetic background identified decreased sociable behavior and enhanced spatial learning (Tabuchi et al., 2007). Sociable behavioral deficits were subsequently reproduced independently by the Sdhof laboratory(Etherton et al., 2011a), followed by our own independent replication of both sociable and spatial learning variations on a genuine 129S2/SvPasCrl genetic background (Jaramillo et al., 2014). A single study by the Crawley laboratory failed to replicate these findings in a similar NL3R451C mutation model on a C57BL6J background (Chadman et al., 2008). This suggested differences due to either genetic background or due to variations in behavioral protocols or experience across laboratories. To address the query of whether genetic background modulates the behavioral phenotype of NL3R451C mutant Linagliptin biological activity mice, we have now examined the same mice characterized by the Crawley laboratory with the NL3R451C mutation on a genuine C57BL6J background. Our findings replicate basically the same behavioral results observed by Chadman et al. On a C57BL6J genetic background, the NL3R451C mouse model does not display sociable deficits or cognitive enhancement seen on either hybrid or genuine 129S2/SvPasCrl genetic backgrounds. Our findings suggest that genetic background can modify behavioral features of the NL3R451C mutation. We conclude that genetic background rather than variations in behavioral screening or experience across laboratories accounts for the discrepant findings in the literature. METHODS Generation of NL3R451C mice NL3R451C on a genuine C57BL6J background (NL3R451Cwere initially generated in Linagliptin biological activity the laboratory of Dr. Nathaniel Heintz on a genuine C57BL6J genetic background (Chadman et al., 2008). Frozen spermatozoa were acquired as a gift from Dr. Heintz, and mice were re-derived by The Jackson Laboratory through fertilization. Mice were subsequently managed on a genuine C57BL6J genetic background. Behavioral Summary Behavioral tests were performed on a cohort of 42 male mice that ranged in age from 2.3 to 6.6 months of age. The cohort was generated by breeding wild-type males with heterozygous females (is an X-linked gene). Mice from the same litter were housed as pairs to ensure similar environmental experiences. Littermate pairs from multiple litters were used to decrease litter-specific effects. Mice were kept on a 12-h light:12-h dark cycle, and behavioral screening was conducted during the light cycle. Behavioral testing started when the mice were between 2C6 weeks of age by an experimenter.