Friday, May 21, 2010
Franklin Hall B Level 4 (Philadelphia Marriott Downtown)
1:00 PM
Background: The etiology and biological markers of autism are not currently known, but strong evidence exists for a genetic component and several synaptic genes have been implicated. SHANK genes encode a family of scaffolding proteins located on the postsynaptic side of excitatory synapses. Mutations in some SHANK genes have been detected in several autistic individuals.
Objectives: To understand the consequences of SHANK mutations relevant to the diagnostic and associated symptoms of autism, comprehensive behavioral phenotyping on a line of shank1 mutant mice was conducted on multiple measures of social interactions, social olfaction, repetitive behaviors, anxiety-related behaviors, and a series of control measures for physical abilities.
Methods: Shank1 mutant mice, generated by Hung et al., 2008 as previously described, were imported to NIMH in Bethesda, MD, and bred as heterozygotes. All experiments were conducted and analyzed by investigators who were uniformed of the genotype during the behavioral tasks. Assays included two anxiety-related tasks (elevated plus-maze and light/dark exploration), open field locomotor activity, a battery of general health parameters, a sequence of neurological reflexes, sensory measures including olfactory habituation/dishabituation, acoustic startle threshold and prepulse inhibition, rotarod coordination and balance, juvenile reciprocal social interactions, and adult social approach (Chadman et al., 2008; Crawley et al., 2008; MacFarlane et al., 2008).
Results: Adult shank1 null, heterozygote, and wildtype littermates displayed no significant differences on adult social approach. Juvenile reciprocal social interactions appeared to show similar scores across genotypes. Shank1 mutants were similar to their wildtype and heterozygous littermates on standardized measures of general health, neurological reflexes and sensory skills including acoustic startle threshold, prepulse inhibition, and pain sensitivity. Locomotor activity in the open field and time spent in the center of the arena were lower in the null mutants, as previously reported (Hung et al., 2008). A partial anxiety-like phenotype was detected in the null mutants in some components of the light/dark task, as previously reported (Hung et al., 2008).
Conclusions: At present, our data indicate normal scores in shank1 mutant mice on behavioral measures relevant to the diagnostic symptoms of autism. Our findings replicate and extend a previous study using other cohorts of shank1 mutant mice (Hung et al., 2008), indicating a moderate anxiety-like phenotype and hypoactivity. Null mutation of the shank1 gene in mice did not produce social deficits on the tasks conducted.
Objectives: To understand the consequences of SHANK mutations relevant to the diagnostic and associated symptoms of autism, comprehensive behavioral phenotyping on a line of shank1 mutant mice was conducted on multiple measures of social interactions, social olfaction, repetitive behaviors, anxiety-related behaviors, and a series of control measures for physical abilities.
Methods: Shank1 mutant mice, generated by Hung et al., 2008 as previously described, were imported to NIMH in Bethesda, MD, and bred as heterozygotes. All experiments were conducted and analyzed by investigators who were uniformed of the genotype during the behavioral tasks. Assays included two anxiety-related tasks (elevated plus-maze and light/dark exploration), open field locomotor activity, a battery of general health parameters, a sequence of neurological reflexes, sensory measures including olfactory habituation/dishabituation, acoustic startle threshold and prepulse inhibition, rotarod coordination and balance, juvenile reciprocal social interactions, and adult social approach (Chadman et al., 2008; Crawley et al., 2008; MacFarlane et al., 2008).
Results: Adult shank1 null, heterozygote, and wildtype littermates displayed no significant differences on adult social approach. Juvenile reciprocal social interactions appeared to show similar scores across genotypes. Shank1 mutants were similar to their wildtype and heterozygous littermates on standardized measures of general health, neurological reflexes and sensory skills including acoustic startle threshold, prepulse inhibition, and pain sensitivity. Locomotor activity in the open field and time spent in the center of the arena were lower in the null mutants, as previously reported (Hung et al., 2008). A partial anxiety-like phenotype was detected in the null mutants in some components of the light/dark task, as previously reported (Hung et al., 2008).
Conclusions: At present, our data indicate normal scores in shank1 mutant mice on behavioral measures relevant to the diagnostic symptoms of autism. Our findings replicate and extend a previous study using other cohorts of shank1 mutant mice (Hung et al., 2008), indicating a moderate anxiety-like phenotype and hypoactivity. Null mutation of the shank1 gene in mice did not produce social deficits on the tasks conducted.
Supported by the National Institute of Mental Health Intramural Research Program.
References:
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).
Hung, A.Y. et al. Smaller dendritic spines, weaker synaptic transmission, but enhanced spatial learning in mice lacking Shank1. J Neurosci 28, 1697-708 (2008).
McFarlane, H.G. et al. Autism-like behavioral phenotypes in BTBR T+tf/J mice. Genes Brain Behav 7, 152-63 (2008).