title: Studying autism in rodent models: reconciling endophenotypes with comorbidities.
abstract: Autism spectrum disorder (ASD) patients commonly exhibit a variety of comorbid traits including seizures, anxiety, aggressive behavior, gastrointestinal problems, motor deficits, abnormal sensory processing, and sleep disturbances for which the cause is unknown. These features impact negatively on daily life and can exaggerate the effects of the core diagnostic traits (social communication deficits and repetitive behaviors). Studying endophenotypes relevant to both core and comorbid features of ASD in rodent models can provide insight into biological mechanisms underlying these disorders. Here we review the characterization of endophenotypes in a selection of environmental, genetic, and behavioral rodent models of ASD. In addition to exhibiting core ASD-like behaviors, each of these animal models display one or more endophenotypes relevant to comorbid features including altered sensory processing, seizure susceptibility, anxiety-like behavior, and disturbed motor functions, suggesting that these traits are indicators of altered biological pathways in ASD. However, the study of behaviors paralleling comorbid traits in animal models of ASD is an emerging field and further research is needed to assess altered gastrointestinal function, aggression, and disorders of sleep onset across models. Future studies should include investigation of these endophenotypes in order to advance our understanding of the etiology of this complex disorder.
authors.affiliation: Department of Medicine, The University of Melbourne , Parkville, VIC , Australia.
authors.forename: Andrew
authors.initials: A
authors.lastname: Argyropoulos
authors.forename: Krista L
authors.initials: KL
authors.lastname: Gilby
authors.forename: Elisa L
authors.initials: EL
authors.lastname: Hill-Yardin
keywords: aggression; anxiety; autism; epilepsy; gastrointestinal function; motor deficits; sensory; sleep
references.citation: Neuropsychopharmacology. 2008 Mar;33(4):901-12
references.pmid: 17507914
references.citation: Am J Hum Genet. 1994 Mar;54(3):464-72
references.pmid: 7906921
references.citation: Behav Brain Res. 2009 Jun 8;200(1):33-41
references.pmid: 19154758
references.citation: Epilepsy Res. 1999 Jul;35(3):183-95
references.pmid: 10413314
references.citation: J Autism Dev Disord. 2007 May;37(5):894-910
references.pmid: 17016677
references.citation: Neurology. 2008 Dec 2;71(23):1923-4
references.pmid: 19047565
references.citation: Trends Neurosci. 2009 Jul;32(7):402-12
references.pmid: 19541375
references.citation: Clin Genet. 2010 Dec;78(6):519-21
references.pmid: 20880122
references.citation: Cell Tissue Res. 2006 Jun;324(3):353-60
references.pmid: 16453106
references.citation: Trends Cogn Sci. 2011 Sep;15(9):409-16
references.pmid: 21855394
references.citation: Genes Brain Behav. 2011 Mar;10(2):228-35
references.pmid: 21040460
references.citation: Mol Autism. 2013 Feb 19;4(1):4
references.pmid: 23422139
references.citation: Brain Cogn. 2006 Jun;61(1):5-13
references.pmid: 16500009
references.citation: Autism Res. 2009 Jun;2(3):157-77
references.pmid: 19598235
references.citation: Nat Rev Neurosci. 2010 Jul;11(7):490-502
references.pmid: 20559336
references.citation: Neuroimage. 2006 Jan 15;29(2):475-84
references.pmid: 16115783
references.citation: Science. 1997 Sep 5;277(5331):1511-5
references.pmid: 9278515
references.citation: Curr Opin Neurobiol. 2012 Jun;22(3):530-6
references.pmid: 22000839
references.citation: Mol Biol Rep. 2013 Apr;40(4):2969-75
references.pmid: 23264101
references.citation: Dev Psychobiol. 2009 May;51(4):345-57
references.pmid: 19365795
references.citation: Proc Natl Acad Sci U S A. 2009 Oct 20;106(42):17998-8003
references.pmid: 19822762
references.citation: Epilepsia. 2011 Feb;52(2):347-57
references.pmid: 21204822
references.citation: Biol Psychiatry. 2010 Dec 15;68(12):1100-6
references.pmid: 21130222
references.citation: J Autism Dev Disord. 2006 Jul;36(5):585-95
references.pmid: 16617404
references.citation: Biol Psychiatry. 2007 Nov 1;62(9):1015-21
references.pmid: 17572391
references.citation: J Med Microbiol. 2005 Oct;54(Pt 10):987-991
references.pmid: 16157555
references.citation: Nature. 2011 Apr 28;472(7344):437-42
references.pmid: 21423165
references.citation: J Physiol. 2009 Feb 1;587(3):567-86
references.pmid: 19064621
references.citation: Eur J Neurosci. 2000 Dec;12(12):4405-16
references.pmid: 11122351
references.citation: Eur Child Adolesc Psychiatry. 2011 Jul;20(7):333-40
references.pmid: 21528391
references.citation: N Engl J Med. 2011 Jul 14;365(2):173-5
references.pmid: 21751912
references.citation: Neuron. 2005 Nov 3;48(3):497-507
references.pmid: 16269366
references.citation: Eur J Neurosci. 2004 Jul;20(2):403-18
references.pmid: 15233750
references.citation: Epilepsy Res. 1999 Jul;35(3):197-209
references.pmid: 10413315
references.citation: J Comp Psychol. 2006 Feb;120(1):19-30
references.pmid: 16551161
references.citation: Neuroscience. 2010 Dec 1;171(2):421-33
references.pmid: 20800661
references.citation: Res Dev Disabil. 2013 Apr;34(4):1256-66
references.pmid: 23417131
references.citation: Neuroscience. 2010 Oct 13;170(2):514-22
references.pmid: 20603192
references.citation: Epilepsy Behav. 2013 Mar;26(3):370-4
references.pmid: 23415480
references.citation: Nat Rev Neurosci. 2004 Jul;5(7):553-64
references.pmid: 15208697
references.citation: Nature. 2012 Jun 13;486(7402):261-5
references.pmid: 22699620
references.citation: N Engl J Med. 2006 Mar 30;354(13):1370-7
references.pmid: 16571880
references.citation: J Autism Dev Disord. 2006 Aug;36(6):779-93
references.pmid: 16609825
references.citation: Curr Opin Neurobiol. 2009 Apr;19(2):231-4
references.pmid: 19545994
references.citation: Annu Rev Med. 2009;60:367-80
references.pmid: 19630577
references.citation: Pediatrics. 2009 Aug;124(2):680-6
references.pmid: 19651585
references.citation: Behav Brain Res. 2007 Jan 10;176(1):53-65
references.pmid: 16890300
references.citation: Clin Child Fam Psychol Rev. 2011 Sep;14(3):302-17
references.pmid: 21735077
references.citation: Sleep. 2006 Dec;29(12):1563-71
references.pmid: 17252887
references.citation: Behav Brain Res. 2008 Mar 17;188(1):178-94
references.pmid: 18068825
references.citation: Front Integr Neurosci. 2011 Jan 05;4:129
references.pmid: 21258617
references.citation: Dev Med Child Neurol. 2005 Aug;47(8):551-5
references.pmid: 16108456
references.citation: Dev Psychobiol. 2004 Sep;45(2):83-92
references.pmid: 15340977
references.citation: Brain Dev. 2010 Oct;32(9):783-9
references.pmid: 20691552
references.citation: Behav Neurosci. 2007 Apr;121(2):370-9
references.pmid: 17469927
references.citation: Trends Cell Biol. 2011 Oct;21(10):594-603
references.pmid: 21840719
references.citation: Brain Pathol. 2007 Oct;17(4):448-59
references.pmid: 17919130
references.citation: Neurology. 2006 Aug 8;67(3):407-12
references.pmid: 16894099
references.citation: Science. 2007 Oct 5;318(5847):71-6
references.pmid: 17823315
references.citation: Epilepsia. 2008 Nov;49 Suppl 8:108-10
references.pmid: 19049604
references.citation: Lancet Neurol. 2008 Mar;7(3):231-45
references.pmid: 18275925
references.citation: Cell. 2009 Apr 3;137(1):159-71
references.pmid: 19345194
references.citation: Neurosci Res. 2007 Feb;57(2):289-95
references.pmid: 17157402
references.citation: Brain Res. 2003 May 2;971(1):47-54
references.pmid: 12691836
references.citation: Neuroscience. 2010 Dec 29;171(4):1197-208
references.pmid: 20888890
references.citation: Cereb Cortex. 2011 May;21(5):1134-46
references.pmid: 20943668
references.citation: Behav Neurosci. 2010 Feb;124(1):106-114
references.pmid: 20141285
references.citation: J Neurosci. 2013 Apr 17;33(16):6776-81
references.pmid: 23595736
references.citation: Behav Brain Res. 2010 Mar 17;208(1):178-88
references.pmid: 19941908
references.citation: Neuropharmacology. 2008 May;54(6):901-11
references.pmid: 18395759
references.citation: Transl Psychiatry. 2013 Jan 22;3:e220
references.pmid: 23340503
references.citation: Nat Rev Neurosci. 2013 May;14(5):337-49
references.pmid: 23595016
references.citation: Epilepsy Behav. 2007 Feb;10(1):8-15
references.pmid: 17027340
references.citation: Toxicol Lett. 2011 Mar 5;201(2):137-42
references.pmid: 21195144
references.citation: Epilepsia. 1999 Dec;40(12):1697-707
references.pmid: 10612332
references.citation: Dev Med Child Neurol. 2012 Apr;54(4):306-12
references.pmid: 22348343
references.citation: Curr Opin Neurol. 2011 Apr;24(2):132-9
references.pmid: 21293268
references.citation: Epilepsia. 2011 Jun;52(6):1071-5
references.pmid: 21671922
references.citation: Epilepsia. 2005;46 Suppl 5:3-9
references.pmid: 15987246
references.citation: Exp Cell Res. 2009 Jul 15;315(12):2001-11
references.pmid: 19371741
references.citation: Dev Med Child Neurol. 2006 Oct;48(10):819-24
references.pmid: 16978461
references.citation: Biol Psychiatry. 2008 Oct 1;64(7):577-82
references.pmid: 18565495
references.citation: Nature. 2008 Oct 16;455(7215):903-11
references.pmid: 18923512
references.citation: Psychopharmacology (Berl). 1988;94(3):335-6
references.pmid: 2833761
references.citation: Seizure. 2007 Jan;16(1):59-68
references.pmid: 17116413
references.citation: Mol Autism. 2010 Dec 17;1(1):15
references.pmid: 21167025
references.citation: Cereb Cortex. 1994 Mar-Apr;4(2):119-28
references.pmid: 8038563
references.citation: Behav Brain Res. 2011 Feb 2;217(1):47-54
references.pmid: 20937326
references.citation: J Neurosci. 2012 Oct 24;32(43):14966-78
references.pmid: 23100419
references.citation: Pharmacol Biochem Behav. 1986 May;24(5):1383-91
references.pmid: 3088608
references.citation: Am J Physiol Gastrointest Liver Physiol. 2007 Mar;292(3):G930-8
references.pmid: 17158255
references.citation: Neuropharmacology. 2004 Oct;47(5):724-33
references.pmid: 15458844
references.citation: Behav Genet. 2010 Mar;40(2):201-10
references.pmid: 20033273
references.citation: Nature. 2012 Apr 29;486(7402):256-60
references.pmid: 22699619
references.citation: Nat Genet. 2003 May;34(1):27-9
references.pmid: 12669065
references.citation: Proc Natl Acad Sci U S A. 2011 Aug 16;108(33):13764-9
references.pmid: 21808020
references.citation: Epilepsy Behav. 2010 Feb;17(2):178-82
references.pmid: 20042370
references.citation: Behav Brain Res. 2007 Jan 10;176(1):149-69
references.pmid: 16950524
references.citation: J Neurochem. 2010 Apr;113(2):515-29
references.pmid: 20405543
references.citation: Semin Pediatr Surg. 2004 Nov;13(4):224-35
references.pmid: 15660316
references.citation: J Med Genet. 2006 Oct;43(10):822-8
references.pmid: 16284256
references.citation: Prog Neurobiol. 1982;19(4):315-59
references.pmid: 6134304
references.citation: Curr Psychiatry Rep. 2013 Feb;15(2):337
references.pmid: 23307560
references.citation: Nature. 2013 Jan 17;493(7432):327-37
references.pmid: 23325215
references.citation: Brain Res. 2011 Mar 22;1380:42-77
references.pmid: 21129364
references.citation: Neuropsychopharmacology. 2005 Jan;30(1):80-9
references.pmid: 15238991
references.citation: J Autism Dev Disord. 2008 Jan;38(1):127-37
references.pmid: 17415630
references.citation: Epilepsy Behav. 2005 May;6(3):312-9
references.pmid: 15820337
references.citation: Behav Genet. 1997 Sep;27(5):465-75
references.pmid: 9336083
references.citation: J Autism Dev Disord. 2011 Jul;41(7):926-37
references.pmid: 20960041
references.citation: Cell. 2011 Sep 30;147(1):235-46
references.pmid: 21962519
references.citation: Pediatrics. 2010 Jan;125 Suppl 1:S19-29
references.pmid: 20048084
references.citation: Genes Brain Behav. 2008 Mar;7(2):152-63
references.pmid: 17559418
references.citation: Nat Genet. 2007 Jan;39(1):25-7
references.pmid: 17173049
references.citation: Science. 2006 Jan 27;311(5760):531-5
references.pmid: 16439662
references.citation: Nat Genet. 2010 Jun;42(6):489-91
references.pmid: 20473310
references.citation: Brain Dev. 2007 Sep;29(8):486-90
references.pmid: 17321709
references.citation: J Sleep Res. 2008 Jun;17(2):197-206
references.pmid: 18482108
references.citation: Hum Mol Genet. 2011 Aug 1;20(15):3093-108
references.pmid: 21558424
references.citation: J Dev Behav Pediatr. 2006 Apr;27(2 Suppl):S128-36
references.pmid: 16685179
references.citation: Curr Opin Neurobiol. 2012 Jun;22(3):412-22
references.pmid: 22424845
references.citation: Behav Brain Res. 2011 Jan 1;216(1):446-51
references.pmid: 20816701
references.citation: J Dev Behav Pediatr. 2011 Jun;32(5):351-60
references.pmid: 21555957
references.citation: J Neurosci. 2002 Sep 1;22(17):7809-17
references.pmid: 12196604
references.citation: Autism Res. 2008 Jun;1(3):147-58
references.pmid: 19360662