title: Histidine decarboxylase knockout mice, a genetic model of Tourette syndrome, show repetitive grooming after induced fear.
abstract: Tics, such as are seen in Tourette syndrome (TS), are common and can cause profound morbidity, but they are poorly understood. Tics are potentiated by psychostimulants, stress, and sleep deprivation. Mutations in the gene histidine decarboxylase (Hdc) have been implicated as a rare genetic cause of TS, and Hdc knockout mice have been validated as a genetic model that recapitulates phenomenological and pathophysiological aspects of the disorder. Tic-like stereotypies in this model have not been observed at baseline but emerge after acute challenge with the psychostimulant d-amphetamine. We tested the ability of an acute stressor to stimulate stereotypies in this model, using tone fear conditioning. Hdc knockout mice acquired conditioned fear normally, as manifested by freezing during the presentation of a tone 48h after it had been paired with a shock. During the 30min following tone presentation, knockout mice showed increased grooming. Heterozygotes exhibited normal freezing and intermediate grooming. These data validate a new paradigm for the examination of tic-like stereotypies in animals without pharmacological challenge and enhance the face validity of the Hdc knockout mouse as a pathophysiologically grounded model of tic disorders.
authors.affiliation: Department of Psychiatry, Yale Univeristy, New Haven, CT, USA.
authors.forename: Meiyu
authors.initials: M
authors.lastname: Xu
authors.affiliation: Department of Psychiatry, Yale Univeristy, New Haven, CT, USA.
authors.forename: Lina
authors.initials: L
authors.lastname: Li
authors.affiliation: Tohoku University, Graduate School of Engineering, Sendai, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Ohtsu
authors.affiliation: Department of Psychiatry, Yale Univeristy, New Haven, CT, USA; Department of Psychology, Yale Univeristy, New Haven, CT, USA; Child Study Center, Yale Univeristy, New Haven, CT, USA; Interdepartmental Neuroscience Program, Yale Univeristy, New Haven, CT, USA. Electronic address: Christopher.pittenger@yale.edu.
authors.forename: Christopher
authors.initials: C
authors.lastname: Pittenger
mesh_terms: D000161:Acoustic Stimulation; D000818:Animals; D003214:Conditioning, Classical; D005239:Fear; D006120:Grooming; D006640:Histidine Decarboxylase / Q000235:genetics*; D018345:Mice, Knockout; D005879:Tourette Syndrome / Q000235:genetics / Q000523:psychology*
chemical_list: D006640:Histidine Decarboxylase
keywords: Histamine; Histidine decarboxylase; Stereotypical behavior; Stress; Tics; Tourette syndrome
references.citation: J Child Adolesc Psychopharmacol. 2010 Aug;20(4):237-47
references.pmid: 20807062
references.citation: Acta Pharmacol Sin. 2010 Nov;31(11):1431-7
references.pmid: 21052083
references.citation: N Engl J Med. 2010 Dec 9;363(24):2332-8
references.pmid: 21142535
references.citation: Eur Child Adolesc Psychiatry. 2011 Apr;20(4):173-96
references.pmid: 21445724
references.citation: Neurosci Lett. 2011 May 16;495(2):110-4
references.pmid: 21440039
references.citation: Curr Opin Genet Dev. 2011 Jun;21(3):302-9
references.pmid: 21277193
references.citation: J Neurosci. 2011 Oct 26;31(43):15340-51
references.pmid: 22031880
references.citation: Am J Psychiatry. 2011 Dec;168(12):1326-37
references.pmid: 21955933
references.citation: J Am Acad Child Adolesc Psychiatry. 2012 Feb;51(2):192-201.e5
references.pmid: 22265365
references.citation: Neurosci Biobehav Rev. 2013 Jul;37(6):1150-6
references.pmid: 23017868
references.citation: Neurosci Biobehav Rev. 2013 Jul;37(6):1085-100
references.pmid: 23583771
references.citation: J Med Genet. 2013 Nov;50(11):760-4
references.pmid: 23825391
references.citation: Eur Neuropsychopharmacol. 2013 Nov;23(11):1423-31
references.pmid: 23876376
references.citation: PLoS Genet. 2013 Oct;9(10):e1003864
references.pmid: 24204291
references.citation: Neuron. 2014 Jan 8;81(1):77-90
references.pmid: 24411733
references.citation: J Neurosci Methods. 2014 Dec 30;238:54-69
references.pmid: 25244952
references.citation: Eur Neuropsychopharmacol. 2014 Dec;24(12):1896-906
references.pmid: 25464894
references.citation: J Psychosom Res. 2015 Mar;78(3):293-8
references.pmid: 25149879
references.citation: Behav Modif. 2014 Mar;38(2):184-216
references.pmid: 24516255
references.citation: Indian J Exp Biol. 2000 Oct;38(10):988-93
references.pmid: 11324170
references.citation: FEBS Lett. 2001 Jul 27;502(1-2):53-6
references.pmid: 11478947
references.citation: Adv Neurol. 2001;85:261-71
references.pmid: 11530433
references.citation: Neuron. 2002 Apr 25;34(3):447-62
references.pmid: 11988175
references.citation: Lancet. 2002 Nov 16;360(9345):1577-86
references.pmid: 12443611
references.citation: Eur J Neurosci. 2004 Aug;20(4):1051-8
references.pmid: 15305873
references.citation: J Neurosci. 2004 Aug 25;24(34):7557-65
references.pmid: 15329403
references.citation: Eur J Pharmacol. 1981 Feb 19;69(4):499-502
references.pmid: 6113966
references.citation: J Neuropsychiatry Clin Neurosci. 1990 Summer;2(3):275-81
references.pmid: 2136086
references.citation: J Child Psychol Psychiatry. 2007 Feb;48(2):157-66
references.pmid: 17300554
references.citation: Biol Psychiatry. 2012 Mar 1;71(5):392-402
references.pmid: 22169095
references.citation: Hippocampus. 2007;17(8):634-41
references.pmid: 17534971
references.citation: Nature. 2007 Aug 23;448(7156):894-900
references.pmid: 17713528
references.citation: Neuropsychopharmacology. 2008 May;33(6):1239-51
references.pmid: 17987065
references.citation: Physiol Rev. 2008 Jul;88(3):1183-241
references.pmid: 18626069
references.citation: Curr Psychiatry Rep. 2008 Aug;10(4):323-30
references.pmid: 18627671
references.citation: Nat Med. 2010 May;16(5):598-602, 1p following 602
references.pmid: 20418887
references.citation: N Engl J Med. 2010 May 20;362(20):1901-8
references.pmid: 20445167