Genetic background effects in Neuroligin‐3 mutant mice: Minimal behavioral abnormalities on C57 background

Abstract

Behavioral symptoms of autism can be highly variable, even in cases that involve identical genetic mutations. Previous studies in mice with a mutation of the Neuroligin-3 gene showed enhanced learning and social deficits. We replicated these findings on the same and different genetic backgrounds. In this study, however, the same mutation in mice on a different genetic background did not reproduce our previous findings. Our results suggest that genetic background influences behavioral symptoms of this autism-associated mutation.

Stage 2 Registered Report: Variation in neurodevelopmental outcomes in children with sex chromosome trisomies: testing the double hit hypothesis

“…This explanation is consistent with rodent research comparing the effect of a NLGN3 mutation between different strains of mouse, suggesting the impact is dependent on the genetic background ( Jaramillo et al ., 2018). It also is compatible with evidence from studies of mutations in NLGN4 in humans, which found that the same mutation may be associated with different phenotypes within one family ( Jamain et al ., 2003; Laumonnier et al ., 2004; Lawson-Yuen et al ., 2008; Yan et al ., 2005).…”

Stage 1 Registered Report: Variation in neurodevelopmental outcomes in children with sex chromosome trisomies: protocol for a test of the double hit hypothesis

“…The wide variation in outcomes suggests that the extra gene dosage could act as a multiplier of other risk factors, which interact with the sex chromosome genes in a dosage-dependent manner and so only assume importance in the subset of individuals who have other genetic or environmental risk factors ( Bishop & Scerif, 2011 ). This explanation is consistent with rodent research comparing the effect of a NLGN3 mutation between different strains of mouse, suggesting the impact is dependent on the genetic background ( Jaramillo et al ., 2017 ). It also is compatible with evidence from studies of mutations in NLGN4 in humans, which found that the same mutation may be associated with different phenotypes within one family ( Jamain et al ., 2003 ; Laumonnier et al ., 2004 ; Lawson-Yuen et al ., 2008 ; Yan et al ., 2005 ).…”

Stage 2 Registered Report: Variation in neurodevelopmental outcomes in children with sex chromosome trisomies: testing the double hit hypothesis

“…The wide variation in outcomes suggests that the extra gene dosage could act as a multiplier of other risk factors, which interact with the sex chromosome genes in a dosage-dependent manner and so only assume importance in the subset of individuals who have other genetic or environmental risk factors ( Bishop & Scerif, 2011 ). This explanation is consistent with rodent research comparing the effect of a NLGN3 mutation between different strains of mouse, suggesting the impact is dependent on the genetic background ( Jaramillo et al ., 2018 ). It also is compatible with evidence from studies of mutations in NLGN4 in humans, which found that the same mutation may be associated with different phenotypes within one family ( Jamain et al ., 2003 ; Laumonnier et al ., 2004 ; Lawson-Yuen et al ., 2008 ; Yan et al ., 2005 ).…”