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Communication impairments in mice lacking Shank1: reduced levels of ultrasonic vocalizations and scent marking behavior.

Wöhr M, Roullet FI, Hung AY, Sheng M, Crawley JN - PLoS ONE (2011)

Bottom Line: In adulthood, genotype affected scent marking behavior in the presence of female urinary pheromones.Adult Shank1(-/-) males deposited fewer scent marks in proximity to female urine than Shank1(+/+) males.Call emission in response to female urinary pheromones also differed between genotypes.

View Article: PubMed Central - PubMed

Affiliation: Laboratory of Behavioral Neuroscience, National Institute of Mental Health, Bethesda, Maryland, United States of America. markus.woehr@staff.uni-marburg.de

ABSTRACT
Autism is a neurodevelopmental disorder with a strong genetic component. Core symptoms are abnormal reciprocal social interactions, qualitative impairments in communication, and repetitive and stereotyped patterns of behavior with restricted interests. Candidate genes for autism include the SHANK gene family, as mutations in SHANK2 and SHANK3 have been detected in several autistic individuals. SHANK genes code for a family of scaffolding proteins located in the postsynaptic density of excitatory synapses. To test the hypothesis that a mutation in SHANK1 contributes to the symptoms of autism, we evaluated Shank1(-/-) mutant mice for behavioral phenotypes with relevance to autism, focusing on social communication. Ultrasonic vocalizations and the deposition of scent marks appear to be two major modes of mouse communication. Our findings revealed evidence for low levels of ultrasonic vocalizations and scent marks in Shank1(-/-) mice as compared to wildtype Shank1(+/+) littermate controls. Shank1(-/-) pups emitted fewer vocalizations than Shank1(+/+) pups when isolated from mother and littermates. In adulthood, genotype affected scent marking behavior in the presence of female urinary pheromones. Adult Shank1(-/-) males deposited fewer scent marks in proximity to female urine than Shank1(+/+) males. Call emission in response to female urinary pheromones also differed between genotypes. Shank1(+/+) mice changed their calling pattern dependent on previous female interactions, while Shank1(-/-) mice were unaffected, indicating a failure of Shank1(-/-) males to learn from a social experience. The reduced levels of ultrasonic vocalizations and scent marking behavior in Shank1(-/-) mice are consistent with a phenotype relevant to social communication deficits in autism.

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Ultrasonic vocalizations in isolated female Shank1 pups.(A) Total number of ultrasonic vocalizations, (B) total calling time, (C) duration of calls, (D) peak frequency, (E) peak amplitude and (F) frequency modulation of calls emitted during the 5 min isolation from mother and littermates. Black bar: Shank1+/+ wildtype littermate control mice; striped bar: Shank1+/− heterozygote mice; white bar: Shank1−/−  mutant mice. Data are presented as means ± standard errors of the mean. * p<0.050 vs. Shank1+/+; # p<0.050 vs. Shank1+/−.
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pone-0020631-g004: Ultrasonic vocalizations in isolated female Shank1 pups.(A) Total number of ultrasonic vocalizations, (B) total calling time, (C) duration of calls, (D) peak frequency, (E) peak amplitude and (F) frequency modulation of calls emitted during the 5 min isolation from mother and littermates. Black bar: Shank1+/+ wildtype littermate control mice; striped bar: Shank1+/− heterozygote mice; white bar: Shank1−/− mutant mice. Data are presented as means ± standard errors of the mean. * p<0.050 vs. Shank1+/+; # p<0.050 vs. Shank1+/−.

Mentions: No differences were detected between male and female pups on the emission of USV (all p-values >0.050). However, there were interactions between sex and genotype for total calling time (F2,137 = 3.367, p = 0.038), peak frequency of calls (F2,137 = 4.957, p = 0.008), and peak amplitude of calls (F2,137 = 6.637, p = 0.002; all other p-values >0.050). For all three call parameters, this interaction is due to the fact that genotype differences were evident only in females and not in males. In females, genotype effects were detected for number of USV emitted (F2,69 = 5.209, p = 0.008; Fig. 4A), total calling time (F2,69 = 5.937, p = 0.004; Fig. 4B), peak frequency (F2,69 = 14.276, p<0.001; Fig. 4D) and peak amplitude (F2,69 = 7.763, p = 0.001; Fig. 4E), while latency to start calling, duration of calls and call frequency modulation were not affected (all p-values >0.050; Fig. 4C & 4F; representative spectrograms: Fig. 5). Female Shank1−/− mutant pups emitted fewer USV than female Shank1+/+ littermate control pups (p = 0.005; all other p-values >0.050), resulting in a lower total calling time in the former (p = 0.003; all other p-values >0.050). Furthermore, female Shank1−/− mutant pups emitted USV that had higher peak frequencies than USV emitted by female Shank1+/− (p = 0.021) and Shank1+/+ littermate control pups (p<0.001), while the latter did not differ (p>0.050). Finally, female Shank1−/− mutant pups emitted USV that had lower peak amplitudes than USV emitted by female Shank1+/+ littermate control pups (p = 0.001; all other p-values >0.050). In males, no genotype effects were detected (all p-values >0.050; Fig. 6).


Communication impairments in mice lacking Shank1: reduced levels of ultrasonic vocalizations and scent marking behavior.

Wöhr M, Roullet FI, Hung AY, Sheng M, Crawley JN - PLoS ONE (2011)

Ultrasonic vocalizations in isolated female Shank1 pups.(A) Total number of ultrasonic vocalizations, (B) total calling time, (C) duration of calls, (D) peak frequency, (E) peak amplitude and (F) frequency modulation of calls emitted during the 5 min isolation from mother and littermates. Black bar: Shank1+/+ wildtype littermate control mice; striped bar: Shank1+/− heterozygote mice; white bar: Shank1−/−  mutant mice. Data are presented as means ± standard errors of the mean. * p<0.050 vs. Shank1+/+; # p<0.050 vs. Shank1+/−.
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Related In: Results  -  Collection

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pone-0020631-g004: Ultrasonic vocalizations in isolated female Shank1 pups.(A) Total number of ultrasonic vocalizations, (B) total calling time, (C) duration of calls, (D) peak frequency, (E) peak amplitude and (F) frequency modulation of calls emitted during the 5 min isolation from mother and littermates. Black bar: Shank1+/+ wildtype littermate control mice; striped bar: Shank1+/− heterozygote mice; white bar: Shank1−/− mutant mice. Data are presented as means ± standard errors of the mean. * p<0.050 vs. Shank1+/+; # p<0.050 vs. Shank1+/−.
Mentions: No differences were detected between male and female pups on the emission of USV (all p-values >0.050). However, there were interactions between sex and genotype for total calling time (F2,137 = 3.367, p = 0.038), peak frequency of calls (F2,137 = 4.957, p = 0.008), and peak amplitude of calls (F2,137 = 6.637, p = 0.002; all other p-values >0.050). For all three call parameters, this interaction is due to the fact that genotype differences were evident only in females and not in males. In females, genotype effects were detected for number of USV emitted (F2,69 = 5.209, p = 0.008; Fig. 4A), total calling time (F2,69 = 5.937, p = 0.004; Fig. 4B), peak frequency (F2,69 = 14.276, p<0.001; Fig. 4D) and peak amplitude (F2,69 = 7.763, p = 0.001; Fig. 4E), while latency to start calling, duration of calls and call frequency modulation were not affected (all p-values >0.050; Fig. 4C & 4F; representative spectrograms: Fig. 5). Female Shank1−/− mutant pups emitted fewer USV than female Shank1+/+ littermate control pups (p = 0.005; all other p-values >0.050), resulting in a lower total calling time in the former (p = 0.003; all other p-values >0.050). Furthermore, female Shank1−/− mutant pups emitted USV that had higher peak frequencies than USV emitted by female Shank1+/− (p = 0.021) and Shank1+/+ littermate control pups (p<0.001), while the latter did not differ (p>0.050). Finally, female Shank1−/− mutant pups emitted USV that had lower peak amplitudes than USV emitted by female Shank1+/+ littermate control pups (p = 0.001; all other p-values >0.050). In males, no genotype effects were detected (all p-values >0.050; Fig. 6).

Bottom Line: In adulthood, genotype affected scent marking behavior in the presence of female urinary pheromones.Adult Shank1(-/-) males deposited fewer scent marks in proximity to female urine than Shank1(+/+) males.Call emission in response to female urinary pheromones also differed between genotypes.

View Article: PubMed Central - PubMed

Affiliation: Laboratory of Behavioral Neuroscience, National Institute of Mental Health, Bethesda, Maryland, United States of America. markus.woehr@staff.uni-marburg.de

ABSTRACT
Autism is a neurodevelopmental disorder with a strong genetic component. Core symptoms are abnormal reciprocal social interactions, qualitative impairments in communication, and repetitive and stereotyped patterns of behavior with restricted interests. Candidate genes for autism include the SHANK gene family, as mutations in SHANK2 and SHANK3 have been detected in several autistic individuals. SHANK genes code for a family of scaffolding proteins located in the postsynaptic density of excitatory synapses. To test the hypothesis that a mutation in SHANK1 contributes to the symptoms of autism, we evaluated Shank1(-/-) mutant mice for behavioral phenotypes with relevance to autism, focusing on social communication. Ultrasonic vocalizations and the deposition of scent marks appear to be two major modes of mouse communication. Our findings revealed evidence for low levels of ultrasonic vocalizations and scent marks in Shank1(-/-) mice as compared to wildtype Shank1(+/+) littermate controls. Shank1(-/-) pups emitted fewer vocalizations than Shank1(+/+) pups when isolated from mother and littermates. In adulthood, genotype affected scent marking behavior in the presence of female urinary pheromones. Adult Shank1(-/-) males deposited fewer scent marks in proximity to female urine than Shank1(+/+) males. Call emission in response to female urinary pheromones also differed between genotypes. Shank1(+/+) mice changed their calling pattern dependent on previous female interactions, while Shank1(-/-) mice were unaffected, indicating a failure of Shank1(-/-) males to learn from a social experience. The reduced levels of ultrasonic vocalizations and scent marking behavior in Shank1(-/-) mice are consistent with a phenotype relevant to social communication deficits in autism.

Show MeSH
Related in: MedlinePlus