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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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Scent marking behavior in the absence and presence of female urine in adult male Shank1 mice.(A) Number of scent marks deposited near (within 10 cm2 around) the female urine spot deposited by male subjects before they had an experience of social interactions with a female, and 7 days after they had a 5 minute experience of social interactions with a female. (B) Time spent in proximity to the female urine spot (10 cm2) by male subjects before they had an experience of social interactions with a female and after female experience. (C) Total number of scent marks deposited throughout the entire open field during the 5 min test session in the open field containing urine from a female C57BL/6J mouse deposited by male subjects before they had an experience of social interactions with a female and after female experience. (D) Total number of scent marks deposited throughout the entire open field during the 60 min habituation session in the clean open field without female urine deposited by male subjects before they had an experience of social interactions with a female and after female experience. 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-g009: Scent marking behavior in the absence and presence of female urine in adult male Shank1 mice.(A) Number of scent marks deposited near (within 10 cm2 around) the female urine spot deposited by male subjects before they had an experience of social interactions with a female, and 7 days after they had a 5 minute experience of social interactions with a female. (B) Time spent in proximity to the female urine spot (10 cm2) by male subjects before they had an experience of social interactions with a female and after female experience. (C) Total number of scent marks deposited throughout the entire open field during the 5 min test session in the open field containing urine from a female C57BL/6J mouse deposited by male subjects before they had an experience of social interactions with a female and after female experience. (D) Total number of scent marks deposited throughout the entire open field during the 60 min habituation session in the clean open field without female urine deposited by male subjects before they had an experience of social interactions with a female and after female experience. 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: Genotypes differed on scent marking behavior in the proximity to the female urine spot (F2,72 = 3.399, p = 0.039; Fig. 9A). Shank1−/− mutant mice deposited fewer urine traces in proximity to the female urine spot, in scent marking tests conducted both before and after female experience, as compared to Shank1+/+ littermate control mice (p = 0.045; all other p-values >0.050). Time spent in proximity to the female urine spot showed similar genotype effects (F2,72 = 8.937, p<0.001; Fig. 9B). Shank1−/− mice spent less time within the area of 10 cm2 around the female urine spot than Shank1+/− (p<0.001) and Shank1+/+ littermate control mice (p = 0.008), while the latter did not differ from each other (p = 0.738). There was no genotype difference in the number of urine traces deposited in the entire open field in the presence of female urine, nor in the absence of female urine when males were initially exposed to the clean open field (F2,72 = 0.597, p = 0.553 and F2,72 = 0.514, p = 0.600, respectively; Fig. 9C & 9D). Prior experience with a female did not affect scent marking behavior and no evidence for an interaction between genotype x female experience was obtained (all p-values >0.050).


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)

Scent marking behavior in the absence and presence of female urine in adult male Shank1 mice.(A) Number of scent marks deposited near (within 10 cm2 around) the female urine spot deposited by male subjects before they had an experience of social interactions with a female, and 7 days after they had a 5 minute experience of social interactions with a female. (B) Time spent in proximity to the female urine spot (10 cm2) by male subjects before they had an experience of social interactions with a female and after female experience. (C) Total number of scent marks deposited throughout the entire open field during the 5 min test session in the open field containing urine from a female C57BL/6J mouse deposited by male subjects before they had an experience of social interactions with a female and after female experience. (D) Total number of scent marks deposited throughout the entire open field during the 60 min habituation session in the clean open field without female urine deposited by male subjects before they had an experience of social interactions with a female and after female experience. 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+/−.
© Copyright Policy
Related In: Results  -  Collection

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getmorefigures.php?uid=PMC3111434&req=5

pone-0020631-g009: Scent marking behavior in the absence and presence of female urine in adult male Shank1 mice.(A) Number of scent marks deposited near (within 10 cm2 around) the female urine spot deposited by male subjects before they had an experience of social interactions with a female, and 7 days after they had a 5 minute experience of social interactions with a female. (B) Time spent in proximity to the female urine spot (10 cm2) by male subjects before they had an experience of social interactions with a female and after female experience. (C) Total number of scent marks deposited throughout the entire open field during the 5 min test session in the open field containing urine from a female C57BL/6J mouse deposited by male subjects before they had an experience of social interactions with a female and after female experience. (D) Total number of scent marks deposited throughout the entire open field during the 60 min habituation session in the clean open field without female urine deposited by male subjects before they had an experience of social interactions with a female and after female experience. 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: Genotypes differed on scent marking behavior in the proximity to the female urine spot (F2,72 = 3.399, p = 0.039; Fig. 9A). Shank1−/− mutant mice deposited fewer urine traces in proximity to the female urine spot, in scent marking tests conducted both before and after female experience, as compared to Shank1+/+ littermate control mice (p = 0.045; all other p-values >0.050). Time spent in proximity to the female urine spot showed similar genotype effects (F2,72 = 8.937, p<0.001; Fig. 9B). Shank1−/− mice spent less time within the area of 10 cm2 around the female urine spot than Shank1+/− (p<0.001) and Shank1+/+ littermate control mice (p = 0.008), while the latter did not differ from each other (p = 0.738). There was no genotype difference in the number of urine traces deposited in the entire open field in the presence of female urine, nor in the absence of female urine when males were initially exposed to the clean open field (F2,72 = 0.597, p = 0.553 and F2,72 = 0.514, p = 0.600, respectively; Fig. 9C & 9D). Prior experience with a female did not affect scent marking behavior and no evidence for an interaction between genotype x female experience was obtained (all p-values >0.050).

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