Mapping the Behavioral Signatures of Shank3b Mice in Both Sexes.

Jingjing Liu, Jialin Ye, Chunyuan Ji, Wenting Ren, Youwei He, Fuqiang Xu, Feng Wang
Author Information
  1. Jingjing Liu: NMPA Key Laboratory for Research and Evaluation of Viral Vector Technology in Cell and Gene Therapy Medicinal Products, Shenzhen-Hong Kong Institute of Brain Science, Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, Shenzhen, 518055, China.
  2. Jialin Ye: Shenzhen Key Lab of Translational Research for Brain Diseases, Translational Research Center for the Nervous System, Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, Shenzhen, 518055, China.
  3. Chunyuan Ji: Shenzhen Key Lab of Translational Research for Brain Diseases, Translational Research Center for the Nervous System, Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, Shenzhen, 518055, China.
  4. Wenting Ren: Shenzhen Key Lab of Translational Research for Brain Diseases, Translational Research Center for the Nervous System, Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, Shenzhen, 518055, China.
  5. Youwei He: NMPA Key Laboratory for Research and Evaluation of Viral Vector Technology in Cell and Gene Therapy Medicinal Products, Shenzhen-Hong Kong Institute of Brain Science, Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, Shenzhen, 518055, China.
  6. Fuqiang Xu: NMPA Key Laboratory for Research and Evaluation of Viral Vector Technology in Cell and Gene Therapy Medicinal Products, Shenzhen-Hong Kong Institute of Brain Science, Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, Shenzhen, 518055, China. fq.xu@siat.ac.cn.
  7. Feng Wang: NMPA Key Laboratory for Research and Evaluation of Viral Vector Technology in Cell and Gene Therapy Medicinal Products, Shenzhen-Hong Kong Institute of Brain Science, Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, Shenzhen, 518055, China. feng.wang@siat.ac.cn. ORCID

Abstract

Autism spectrum disorders (ASD) are characterized by social and repetitive abnormalities. Although the ASD mouse model with Shank3b mutations is widely used in ASD research, the behavioral phenotype of this model has not been fully elucidated. Here, a 3D-motion capture system and linear discriminant analysis were used to comprehensively record and analyze the behavioral patterns of male and female Shank3b mutant mice. It was found that both sexes replicated the core and accompanied symptoms of ASD, with significant sex differences. Further, Shank3b heterozygous knockout mice exhibited distinct autistic behaviors, that were significantly different from those those observed in the wild type and homozygous knockout groups. Our findings provide evidence for the inclusion of both sexes and experimental approaches to efficiently characterize heterozygous transgenic models, which are more clinically relevant in autistic studies.

Keywords

References

  1. Neuron. 2014 Sep 3;83(5):1131-43 [PMID: 25155956]
  2. Neurobiol Stress. 2021 Nov 12;15:100417 [PMID: 34815987]
  3. J Child Psychol Psychiatry. 2010 Apr;51(4):432-58 [PMID: 20085609]
  4. Mol Autism. 2021 Jan 19;12(1):2 [PMID: 33468258]
  5. Nat Commun. 2021 May 13;12(1):2784 [PMID: 33986265]
  6. eNeuro. 2018 Oct 5;5(3): [PMID: 30302388]
  7. J Neurosci. 2015 Jul 1;35(26):9648-65 [PMID: 26134648]
  8. J Child Psychol Psychiatry. 2016 May;57(5):585-95 [PMID: 26709141]
  9. Neuron. 2015 Dec 16;88(6):1121-1135 [PMID: 26687221]
  10. Nat Genet. 2014 Aug;46(8):881-5 [PMID: 25038753]
  11. PLoS Genet. 2014 Sep 04;10(9):e1004580 [PMID: 25188300]
  12. Autism Res. 2016 Mar;9(3):350-75 [PMID: 26559786]
  13. Nat Neurosci. 2020 Apr;23(4):520-532 [PMID: 32123378]
  14. Nat Neurosci. 2016 May;19(5):716-724 [PMID: 26928064]
  15. Nat Rev Neurosci. 2010 Jul;11(7):490-502 [PMID: 20559336]
  16. Am J Hum Genet. 2007 Dec;81(6):1289-97 [PMID: 17999366]
  17. Neuropsychopharmacology. 2010 Mar;35(4):976-89 [PMID: 20032969]
  18. Nat Genet. 2019 Mar;51(3):431-444 [PMID: 30804558]
  19. JAMA Psychiatry. 2015 May;72(5):415-23 [PMID: 25738232]
  20. Cereb Cortex. 2022 Jul 12;32(14):3042-3056 [PMID: 34791077]
  21. Pediatr Res. 2009 Jun;65(6):591-8 [PMID: 19218885]
  22. Nature. 2011 Apr 28;472(7344):437-42 [PMID: 21423165]
  23. J Autism Dev Disord. 2010 Oct;40(10):1227-40 [PMID: 20195737]
  24. Front Cell Neurosci. 2019 Mar 26;13:111 [PMID: 30971895]
  25. Nat Commun. 2023 Mar 29;14(1):1750 [PMID: 36991001]
  26. Nature. 2019 Jun;570(7761):326-331 [PMID: 31189958]
  27. Codas. 2013;25(2):191-2 [PMID: 24413388]
  28. Cell Rep. 2019 Nov 12;29(7):2016-2027.e4 [PMID: 31722214]
  29. J Am Acad Child Adolesc Psychiatry. 2017 Jun;56(6):466-474 [PMID: 28545751]
  30. Soc Psychiatry Psychiatr Epidemiol. 2011 Dec;46(12):1283-93 [PMID: 20938640]
  31. Int J Neuropsychopharmacol. 2018 Sep 1;21(9):871-882 [PMID: 29762671]
  32. Nat Biomed Eng. 2019 Nov;3(11):930-942 [PMID: 31110290]
  33. J Child Psychol Psychiatry. 1977 Sep;18(4):297-321 [PMID: 562353]
  34. Neurosci Bull. 2022 Mar;38(3):303-317 [PMID: 34637091]
  35. J Neurosci. 2013 Nov 20;33(47):18448-68 [PMID: 24259569]
  36. MMWR Surveill Summ. 2021 Dec 03;70(11):1-16 [PMID: 34855725]
  37. Cell Rep. 2022 Jan 11;38(2):110231 [PMID: 35021077]
  38. Elife. 2018 Mar 28;7: [PMID: 29589829]
  39. J Autism Dev Disord. 2003 Aug;33(4):365-82 [PMID: 12959416]
  40. Curr Biol. 2023 Apr 10;33(7):1358-1364.e4 [PMID: 36889318]
  41. Nat Genet. 2007 Jan;39(1):25-7 [PMID: 17173049]
  42. J Neurosci. 2010 Feb 10;30(6):2115-29 [PMID: 20147539]
  43. Nat Commun. 2021 May 31;12(1):3321 [PMID: 34059669]
  44. Hum Mol Genet. 2011 Aug 1;20(15):3093-108 [PMID: 21558424]
  45. Psychol Med. 1995 Jan;25(1):63-77 [PMID: 7792363]
  46. Mol Autism. 2017 Jun 15;8:26 [PMID: 28638591]
  47. Cold Spring Harb Symp Quant Biol. 2007;72:645-54 [PMID: 18419324]
  48. BMC Biol. 2022 Dec 15;20(1):281 [PMID: 36522765]

MeSH Term

Animals
Male
Female
Nerve Tissue Proteins
Autism Spectrum Disorder
Mice
Disease Models, Animal
Mice, Knockout
Behavior, Animal
Microfilament Proteins
Mice, Inbred C57BL
Sex Characteristics

Chemicals

Nerve Tissue Proteins
Shank3 protein, mouse
Microfilament Proteins

Word Cloud

Created with Highcharts 10.0.0Shank3bASDAutismmodelusedbehavioralsystemmicesexesdifferencesheterozygousknockoutautisticspectrumdisorderscharacterizedsocialrepetitiveabnormalitiesAlthoughmousemutationswidelyresearchphenotypefullyelucidated3D-motioncapturelineardiscriminantanalysiscomprehensivelyrecordanalyzepatternsmalefemalemutantfoundreplicatedcoreaccompaniedsymptomssignificantsexexhibiteddistinctbehaviorssignificantlydifferentobservedwildtypehomozygousgroupsfindingsprovideevidenceinclusionexperimentalapproachesefficientlycharacterizetransgenicmodelsclinicallyrelevantstudiesMappingBehavioralSignaturesMiceSexes3Danimalmotion-captureComputationalethologySexSpontaneousbehavior

Similar Articles

Cited By