Objectives: To understand the consequences of Nlgn2 mutations relevant to the diagnostic and associated symptoms of autism, comprehensive behavioral phenotyping on a line of Neuroligin-2 (Nlgn2) mutant mice was conducted on multiple measures of social interactions, olfactory communication, repetitive behaviors, anxiety-related behaviors, neurodevelopmental milestones, and a series of control measures for physical abilities.
Methods: Nlgn2 knockout (KO) mice were the generous gift of Nils Brose from the Max-Planck-Institute for Experimental Medicine, Göttingen, Germany. Nlgn2 male and female littermates from heterozygous breeding pairs were used for behavioral studies. Developmental milestones, elevated plus-maze and light/dark anxiety related behaviors, a general health battery, neurological reflexes, sensory measures including olfactory habituation/dishabituation, acoustic startle threshold and prepulse inhibition, motor functions including open field locomotion and rotarod, juvenile reciprocal social interactions and adult social approach were assayed in Nlgn2 knockout, wildtype, and heterozygous mice, using methods previously described (Crawley, 2008; McFarlane et al., 2008; Chadman et al., 2008).
Results: Adult Nlgn2 null mutants did not differ from their wildtype and heterozygote littermates on standardized measures of general health, neurological reflexes, hot plate and tail flick pain sensitivity tasks, or open field activity. Adult social approach did not differ across genotypes. No motor stereotypies or repetitive behaviors were detected in any genotype. A trend toward higher anxiety-like scores was detected in the light/dark task, but not in the elevated plus-maze. Results are in progress for developmental milestones and juvenile reciprocal social interactions.
Conclusions: At present, our data indicate normal scores in Nlgn2 mutant mice on behavioral measures relevant to the diagnostic symptoms of autism. These findings extend and generally confirm previous reports using other cohorts of Nlgn2 mutant mice (Hines et al., 2008; Blundell et al., 2009).
Keywords: neuroligin, animal model, social behavior
References:
Blundell, J. et al. Increased anxiety-like behavior in mice lacking the inhibitory synapse cell adhesion molecule neuroligin 2. Genes Brain Behav 8, 114-26 (2009).
Chadman, K.K. et al. Minimal aberrant behavioral phenotypes of neuroligin-3 R451C knockin mice. Autism Res 1, 147-58 (2008).
Crawley, J.N. Behavioral phenotyping strategies for mutant mice. Neuron 57, 809-18 (2008).
Hines, R.M. et al. Synaptic imbalance, stereotypies, and impaired social interactions in mice with altered neuroligin 2 expression. J Neurosci 28, 6055-67 (2008).
McFarlane, H.G. et al. Autism-like behavioral phenotypes in BTBR T+tf/J mice. Genes Brain Behav 7, 152-63 (2008).