Age-related changes in behavior in C57BL/6J mice from young adulthood to middle age

Molecular Brain

Volumn 9, Issue 1, 2016, Pages

  Shoji, Hirotaka ^a,b   Takao, Keizo ^b,c   Hattori, Satoko ^a,b   Miyakawa, Tsuyoshi ^a,b,c  

^a FUJITA HEALTH UNIVERSITY   (Japan)

^b JAPAN SCIENCE AND TECHNOLOGY AGENCY   (Japan)

^c NATIONAL INSTITUTE FOR PHYSIOLOGICAL SCIENCES   (Japan)

Author keywords

Aging; Behavior; Behavioral test battery; C57BL 6J; Mice

Indexed keywords

ADULT; AGE; ANIMAL EXPERIMENT; ANXIETY ASSESSMENT; ANXIETY DISORDER; ARTICLE; BARNES MAZE TEST; BEHAVIOR CHANGE; BODY TEMPERATURE; BODY WEIGHT; CONTEXTUAL FEAR MEMORY; CONTROLLED STUDY; CUED FEAR MEMORY; DEPRESSION; ELEVATED PLUS MAZE TEST; FEAR CONDITIONING TEST; FORCED SWIM TEST; GRIP STRENGTH; GROUPS BY AGE; HOT PLATE TEST; IMMOBILITY; LIGHT DARK TRANSITION TEST; LOCOMOTION; MEMORY; MIDDLE AGED; MOTOR DYSFUNCTION; MOTOR PERFORMANCE; MOUSE; NEUROMUSCULAR STRENGTH; NOCICEPTION; NONHUMAN; OPEN FIELD TEST; PORSOLT FORCED SWIM TEST; PREPULSE INHIBITION; PRIORITY JOURNAL; ROTAROD TEST; SOCIAL BEHAVIOR; SOCIAL INTERACTION TEST; SPATIAL LEARNING; SPATIAL MEMORY; STARTLE REFLEX; STRENGTH; TAIL SUSPENSION TEST; YOUNG ADULT; AGING; ANIMAL; ANIMAL BEHAVIOR; ANXIETY; C57BL MOUSE; FEAR; IMMOBILIZATION; MOTOR ACTIVITY; MUSCLE STRENGTH; PAIN; PATHOPHYSIOLOGY; PHYSIOLOGY;

AGING; ANIMALS; ANXIETY; BEHAVIOR, ANIMAL; BODY WEIGHT; FEAR; IMMOBILIZATION; MEMORY; MICE, INBRED C57BL; MOTOR ACTIVITY; MUSCLE STRENGTH; PAIN; PREPULSE INHIBITION; REFLEX, STARTLE; SOCIAL BEHAVIOR; SPATIAL LEARNING;

EID: 84955492841     PISSN: None     EISSN: 17566606     Source Type: Journal    
DOI: 10.1186/s13041-016-0191-9     Document Type: Article

References (114)

1. Bishop NA, Lu T, Yankner BA. Neural mechanisms of ageing and cognitive decline. Nature. 2010;464:529-35.
2. Burke SN, Barnes CA. Neural plasticity in the ageing brain. Nat Rev Neurosci. 2006;7:30-40.
3. Mattson MP, Chan SL, Duan W. Modification of brain aging and neurodegenerative disorders by genes, diet, and behavior. Physiol Rev. 2002;82:637-72.
4. Ammassari-Teule M, Fagioli S, Rossi-Arnaud C. Radial maze performance and open-field behaviours in aged C57BL/6 mice: further evidence for preserved cognitive abilities during senescence. Physiol Behav. 1994;55:341-5.
5. Brennan MJ, Dallob A, Friedman E. Involvement of hippocampal serotonergic activity in age-related changes in exploratory behavior. Neurobiol Aging. 1981;2:199-203.
6. Fahlström A, Zeberg H, Ulfhake B. Changes in behaviors of male C57BL/6J mice across adult life span and effects of dietary restriction. Age. 2012;34:1435-52.
7. Flood JF, Morley JE. Pharmacological enhancement of long-term memory retention in old mice. J Gerontol. 1990;45:B101-4.
8. Fordyce DE, Whner JM. Effects of aging on spatial learning and hippocampal protein kinase C in mice. Neurobiol Aging. 1993;14:309-17.
9. Forster MJ, Dubey A, Dawson KM, Stutts WA, Lal H, Sohal RS. Age-related losses of cognitive function and motor skills in mice are associated with oxidative protein damage in the brain. Proc Natl Acad Sci. 1996;93:4765-9.
10. Frick KM, Burlingame LA, Arters JA, Berger-Sweeney J. Reference memory, anxiety and estrous cyclicity in C57BL/6NIA mice are affected by age and sex. Neuroscience. 1999;95:293-307.
11. Hengemihle JM, Long JM, Betkey J, Jucker M, Ingram DK. Age-related psychomotor and spatial learning deficits in 129/SvJ mice. Neurobiol Aging. 1999;20:9-18.
12. Ingram DK, London ED, Reynolds MA, Waller SB, Goodrick CL. Differential effects of age on motor performance in two mouse strains. Neurobiol Aging. 1981;2:221-7.
13. Sprott RL, Eleftheriou BE. Open-field behavior in aging inbred mice. Gerontology. 1974;20:155-62.
14. Chesselet MF, Richter F. Modelling of Parkinson's disease in mice. Lancet Neurol. 2011;10:1108-18.
15. Hall AM, Roberson ED. Mouse models of Alzheimer's disease. Brain Res Bull. 2012;88:3-12.
16. Crawley JN. Behavioral phenotyping strategies for mutant mice. Neuron. 2008;57:809-18.
17. Crawley JN, Paylor R. A proposed test battery and constellations of specific behavioral paradigms to investigate the behavioral phenotypes of transgenic and knockout mice. Horm Behav. 1997;31:197-211.
18. Karl T, Pabst R, von Hörsten S. Behavioral phenotyping of mice in pharmacological and toxicological research. Exp Toxicol Pathol. 2003;55:69-83.
19. Powell CM, Miyakawa T. Schizophrenia-relevant behavioral testing in rodent models: a uniquely human disorder? Biol Psychiatry. 2006;59:1198-207.
20. Rogers DC, Fisher EMC, Brown SDM, Peters J, Hunter AJ, Martin JE. Behavioral and functional analysis of mouse phenotype: SHIRPA, a proposed protocol for comprehensive phenotype assessment. Mamm Genome. 1997;8:711-3.
21. Takao K, Yamasaki N, Miyakawa T. Impact of brain-behavior phenotypying of genetically-engineered mice on research of neuropsychiatric disorders. Neurosci Res. 2007;58:124-32.
22. Crabbe JC, Wahlsten D, Dudek BC. Genetics of mouse behavior: interactions with laboratory environment. Science. 1999;284:1670-2.
23. Holmes A, Iles JP, Mayell SJ, Rodgers RJ. Prior test experience compromises the anxiolytic efficacy of chlordiazepoxide in the mouse light/dark exploration test. Behav Brain Res. 2001;122:159-67.
24. McIlwain KL, Merriweather MY, Yuva-Paylor LA, Paylor R. The use of behavioral test batteries: effects of training history. Physiol Behav. 2001;73:705-17.
25. Wahlsten D, Metten P, Phillips TJ, Boehm SL, Burkhart-Kasch S, Dorow J, et al. Different data from different labs: lessons from studies of gene-environment interaction. J Neurobiol. 2003;54:283-311.
26. Voikar V, Vasar E, Rauvala H. Behavioral alterations induced by repeated testing in C57BL/6J and 129S2/Sv mice: implications for phenotyping screens. Genes Brain Behav. 2004;3:27-38.
27. Matsuo N, Takao K, Nakanishi K, Yamasaki N, Tanda K, Miyakawa T. Behavioral profiles of three C57BL/6 substrains. Front Behav Neurosci. 2010;4:29.
28. Holmes A, Yang RJ, Murphy DL, Crawley JN. Evaluation of antidepressant-related behavioral responses in mice lacking the serotonin transporter. Neuropsychopharmacology. 2002;27:914-23.
29. McFadyen MP, Kusek G, Bolivar VJ, Flaherty L. Differences among eight inbred strains of mice in motor ability and motor learning on a rotorod. Genes Brain Behav. 2003;2:214-9.
30. Prut L, Belzung C. The open field as a paradigm to measure the effects of drugs on anxiety-like behaviors: a review. Eur J Pharmacol. 2003;463:3-33.
31. Frankland PW, O'Brien C, Ohno M, Kirkwood A, Silva AJ. α-CaMKII-dependent plasticity in the cortex is required for permanent memory. Nature. 2001;411:309-13.
32. Anagnostaras SG, Wood SC, Shuman T, Cai DJ, LeDuc AD, Zurn KR, et al. Automated assessment of pavlovian conditioned freezing and shock reactivity in mice using the video freeze system. Front Behav Neurosci. 2010;4:158.
33. Butterfield NN, Graf P, Ries CR, MacLeod BA. The effect of repeated isoflurane anesthesia on spatial and psychomotor performance in young and aged mice. Anesth Analg. 2004;98:1305-11.
34. Halloran BP, Ferguson VL, Simske SJ, Burghardt A, Venton LL, Majumdar S. Changes in bone structure and mass with advancing age in the male C57BL/6J mouse. J Bone Miner Res. 2002;17:1044-50.
35. Talan M. Body temperature of C57BL/6J mice with age. Exp Gerontol. 1984;19:25-9.
36. Talan MI, Engel BT. Temporal decrease of body temperature in middle-aged C57BL/6J mice. J Gerontol. 1986;41:8-12.
37. Shukitt-Hale B, Smith DE, Meydani M, Joseph JA. The effects of dietary antioxidants on psychomotor performance in aged mice. Exp Gerontol. 1999;34:797-808.
38. Serradj N, Jamon M. Age-related changes in the motricity of the inbred mice strains 129/sv and C57BL/6j. Behav Brain Res. 2007;177:80-9.
39. Shc prevents age-dependent increases in emotionality and pain sensitivity in mice. Exp Gerontol. 2007;42:37-45.
40. Matzel LD, Grossman H, Light K, Townsend D, Kolata S. Age-related declines in general cognitive abilities of Balb/C mice are associated with disparities in working memory, body weight, and general activity. Learn Mem. 2008;15:733-46.
41. Webster GW, Shuster L, Eleftheriou BE. Morphine analgesia in mice of different ages. Exp Aging Res. 1976;2:221-33.
42. Benice TS, Rizk A, Kohama S, Pfankuch T, Raber J. Sex-differences in age-related cognitive decline in C57BL/6J mice associated with increased brain microtubule-associated protein 2 and synaptophysin immunoreactivity. Neuroscience. 2006;137:413-23.
43. -/- mice. Behav Brain Res. 2012;229:21-8.
44. Lalonde R, Strazielle C. Exploratory activity and motor coordination in old versus middle-aged C57BL/6J mice. Arch Gerontol Geriatr. 2009;49:39-42.
45. Belzung C, Griebel G. Measuring normal and pathological anxiety-like behaviour in mice: a review. Behav Brain Res. 2001;125:141-9.
46. Bourin M, Hascoet M. The mouse light/dark box test. Eur J Pharmacol. 2003;463:55-65.
47. File SE, Seth P. A review of 25 years of the social interaction test. Eur J Pharmacol. 2003;463:35-53.
48. Walf AA, Frye CA. The use of the elevated plus maze as an assay of anxiety-related behavior in rodents. Nat Protoc. 2007;2:322-8.
49. Griebel G, Belzung C, Perrault G, Sanger DJ. Differences in anxiety-related behaviours and in sensitivity to diazepam in inbred and outbred strains of mice. Psychopharmacology (Berl). 2000;148:164-70.
50. Hattori S, Takao K, Tanda K, Toyama K, Shintani N, Baba A, et al. Comprehensive behavioral analysis of pituitary adenylate cyclase-activating polypeptide (PACAP) knockout mice. Front Behav Neurosci. 2011;6:58.
51. Miyakawa T, Leiter LM, Gerber DJ, Gainetdinov RR, Sotnikova TD, Zeng H, et al. Conditional calcineurin knockout mice exhibit multiple abnormal behaviors related to schizophrenia. Proc Natl Acad Sci. 2003;100:8987-92.
52. Takao K, Kobayashi K, Hagihara H, Ohira K, Shoji H, Hattori S, et al. Deficiency of Schnurri-2, an MHC enhancer binding protein, induces mild chronic inflammation in the brain and confers molecular, neuronal, and behavioral phenotypes related to schizophrenia. Neuropsychopharmacology. 2013;38:1409-25.
53. Belzung C, Le Pape G. Comparison of different behavioral test situations used in psychopharmacology for measurement of anxiety. Physiol Behav. 1994;56:623-8.
54. Milner LC, Crabbe JC. Three murine anxiety models: results from multiple inbred strain comparisons. Genes Brain Behav. 2008;7:496-505.
55. Holmes A, Parmigiani S, Ferrari PF, Palanza P, Rodgers RJ. Behavioral profile of wild mice in the elevated plus-maze test for anxiety. Physiol Behav. 2000;71:509-16.
56. Algeri S, Biagini L, Garofalo P, Marconi M, Pitsikas N, Sacchetti G. Adrenocortical and central monoaminergic system responses to different stressful situations in young and senescent rats. Psychobiol Stress. 1990;54:183-90.
57. Herman JP, Larson BR, Speert DB, Seasholtz AF. Hypothalamo-pituitary adrenocortical dysregulation in aging F344/Brown-Norway F1 hybrid rats. Neurobiol Aging. 2001;22:323-32.
58. Küçük A, Gölgeli A, Saraymen R, Koç N. Effects of age and anxiety on learning and memory. Behav Brain Res. 2008;195:147-52.
59. Francia N, Cirulli F, Chiarotti F, Antonelli A, Aloe L, Alleva E. Spatial memory deficits in middle-aged mice correlate with lower exploratory activity and a subordinate status: role of hippocampal neurotrophins. Eur J Neurosci. 2006;23:711-28.
60. Malatynska E, Steinbusch HW, Redkozubova O, Bolkunov A, Kubatiev A, Yeritsyan NB, et al. Anhedonic-like traits and lack of affective deficits in 18-month-old C57BL/6 mice: implications for modeling elderly depression. Exp Gerontol. 2012;47:552-64.
61. Bedrosian TA, Herring KL, Weil ZM, Nelson RJ. Altered temporal patterns of anxiety in aged and amyloid precursor protein (APP) transgenic mice. Proc Natl Acad Sci. 2011;108:11686-91.
62. Schulz D, Huston JP, Buddenberg T, Topic B. "Despair" induced by extinction trials in the water maze: Relationship with measures of anxiety in aged and adult rats. Neurobiol Learn Mem. 2007;87:309-23.
63. Salchner P, Lubec G, Singewald N. Decreased social interaction in aged rats may not reflect changes in anxiety-related behaviour. Behav Brain Res. 2004;151:1-8.
64. Shoji H, Mizoguchi K. Aging-related changes in the effects of social isolation on social behavior in rats. Physiol Behav. 2011;102:58-62.
65. Keithley EM, Canto C, Zheng QY, Fischel-Ghodsian N, Johnson KR. Age-related hearing loss and the ahl locus in mice. Hear Res. 2004;188:21-8.
66. Ouagazzal AM, Reiss D, Romand R. Effects of age-related hearing loss on startle reflex and prepulse inhibition in mice on pure and mixed C57BL and 129 genetic background. Behav Brain Res. 2006;172:307-15.
67. Willott JF, Carlson S, Chen H. Prepulse inhibition of the startle response in mice: relationship to hearing loss and auditory system plasticity. Behav Neurosci. 1994;108:703-13.
68. David DJP, Bourin M, Hascoët M, Colombel MC, Baker GB, Jolliet P. Comparison of antidepressant activity in 4-and 40-week-old male mice in the forced swimming test: involvement of 5-HT1A and 5-HT1B receptors in old mice. Psychopharmacology (Berl). 2001;153:443-9.
69. Godbout JP, Moreau M, Lestage J, Chen J, Sparkman NL, O'Connor J, et al. Aging exacerbates depressive-like behavior in mice in response to activation of the peripheral innate immune system. Neuropsychopharmacology. 2008;33:2341-51.
70. Kasckow JW, Segar TM, Xiao C, Furay AR, Evanson NK, Ostrander MM, et al. Stability of neuroendocrine and behavioral responsiveness in aging Fischer 344/Brown-Norway hybrid rats. Endocrinology. 2005;146:3105-12.
71. Moretti M, de Souza AG, de Chaves G, de Andrade VM, Romao PRT, Gavioli EC, et al. Emotional behavior in middle-aged rats: implications for geriatric psychopathologies. Physiol Behav. 2011;102:115-20.
72. Ohashi S, Mori A, Kurihara N, Mitsumoto Y, Nakai M. Age-related severity of dopaminergic neurodegeneration to MPTP neurotoxicity causes motor dysfunction in C57BL/6 mice. Neurosci Lett. 2006;401:183-7.
73. Bertoglio LJ, Carobrez AP. Previous maze experience required to increase open arms avoidance in rats submitted to the elevated plus-maze model of anxiety. Behav Brain Res. 2000;108:197-203.
74. Brett RR, Pratt JA. Chronic handling modifies the anxiolytic effect of diazepam in the elevated plus-maze. Eur J Pharmacol. 1990;178:135-8.
75. Korte SM, De Boer SF. A robust animal model of state anxiety: fear-potentiated behaviour in the elevated plus-maze. Eur J Pharmacol. 2003;463:163-75.
76. Schmitt U, Hiemke C. Strain differences in open-field and elevated plus-maze behavior of rats without and with pretest handling. Pharmacol Biochem Behav. 1998;59:807-11.
77. Swiergiel AH, Leskov IL, Dunn AJ. Effects of chronic and acute stressors and CRF on depression-like behavior in mice. Behav Brain Res. 2008;186:32-40.
78. Barnes CA. Memory deficits associated with senescence: a neurophysiological and behavioral study in the rat. J Comp Physiol Psychol. 1979;93:74-104.
79. Kennard JA, Woodruff-Pak DS. Age sensitivity of behavioral tests and brain substrates of normal aging in mice. Front Aging Neurosci. 2011;3:9.
80. Bellush LL, Wright AM, Walker JP, Kopchick J, Colvin RA. Caloric restriction and spatial learning in old mice. Physiol Behav. 1996;60:541-7.
81. Gower AJ, Lamberty Y. The aged mouse as a model of cognitive decline with special emphasis on studies in NMRI mice. Behav Brain Res. 1993;57:163-73.
82. Harburger LL, Lambert TJ, Frick KM. Age-dependent effects of environmental enrichment on spatial reference memory in male mice. Behav Brain Res. 2007;185:43-8.
83. Magnusson KR, Scruggs B, Aniya J, Wright KC, Ontl T, Xing Y, et al. Age-related deficits in mice performing working memory tasks in a water maze. Behav Neurosci. 2003;117:485.
84. Van Praag H, Shubert T, Zhao C, Gage FH. Exercise enhances learning and hippocampal neurogenesis in aged mice. J Neurosci. 2005;25:8680-5.
85. Wong AA, Brown RE. Age-related changes in visual acuity, learning and memory in C57BL/6J and DBA/2J mice. Neurobiol Aging. 2007;28:1577-93.
86. Klapdor K, Van Der Staay FJ. The Morris water-escape task in mice: strain differences and effects of intra-maze contrast and brightness. Physiol Behav. 1997;60:1247-54.
87. Harrison FE, Hosseini AH, McDonald MP. Endogenous anxiety and stress responses in water maze and Barnes maze spatial memory tasks. Behav Brain Res. 2009;198:247-51.
88. Whishaw IQ, Tomie JA. Of mice and mazes: similarities between mice and rats on dry land but not water mazes. Physiol Behav. 1997;60:1191-7.
89. Bach ME, Barad M, Son H, Zhuo M, Lu YF, Shih R, et al. Age-related defects in spatial memory are correlated with defects in the late phase of hippocampal long-term potentiation in vitro and are attenuated by drugs that enhance the cAMP signaling pathway. Proc Natl Acad Sci. 1999;96:5280-5.
90. Bergado JA, Almaguer W, Rojas Y, Capdevila V, Frey JU. Spatial and emotional memory in aged rats: a behavioral-statistical analysis. Neuroscience. 2011;172:256-69.
91. Doyère V, Gisquet-Verrier P, de Marsanich B, Ammassari-Teule M. Age-related modifications of contextual information processing in rats: role of emotional reactivity, arousal and testing procedure. Behav Brain Res. 2000;114:153-65.
92. Gould TJ, Feiro OR. Age-related deficits in the retention of memories for cued fear conditioning are reversed by galantamine treatment. Behav Brain Res. 2005;165:160-71.
93. Houston FP, Stevenson GD, McNaughton BL, Barnes CA. Effects of age on the generalization and incubation of memory in the F344 rat. Learn Mem. 1999;6:111-9.
94. Kaczorowski CC, Disterhoft JF. Memory deficits are associated with impaired ability to modulate neuronal excitability in middle-aged mice. Learn Mem. 2009;16:362-6.
95. Woodruff-Pak DS, Foy MR, Akopian GG, Lee KH, Zach J, Nguyen KP, et al. Differential effects and rates of normal aging in cerebellum and hippocampus. Proc Natl Acad Sci. 2010;107:1624-9.
96. Foster TC, DeFazio RA, Bizon JL. Characterizing cognitive aging of spatial and contextual memory in animal models. Front Aging Neurosci. 2012;4:12.
97. Fukushima H, Maeda R, Suzuki R, Suzuki A, Nomoto M, Toyoda H, et al. Upregulation of calcium/calmodulin-dependent protein kinase IV improves memory formation and rescues memory loss with aging. J Neurosci. 2008;28:9910-9.
98. Peleg S, Sananbenesi F, Zovoilis A, Burkhardt S, Bahari-Javan S, Agis-Balboa RC, et al. Altered histone acetylation is associated with age-dependent memory impairment in mice. Science. 2010;328:753-6.
99. Mora F, Segovia G, del Arco A. Aging, plasticity and environmental enrichment: structural changes and neurotransmitter dynamics in several areas of the brain. Brain Res Rev. 2007;55:78-88.
100. Rosenzweig ES, Barnes CA. Impact of aging on hippocampal function: plasticity, network dynamics, and cognition. Prog Neurobiol. 2003;69:143-79.
101. Miyakawa T, Yamada M, Duttaroy A, Wess J. Hyperactivity and intact hippocampus-dependent learning in mice lacking the M1 muscarinic acetylcholine receptor. J Neurosci. 2001;21:5239-50.
102. Ohira K, Kobayashi K, Toyama K, Nakamura HK, Shoji H, Takao K, et al. Synaptosomal-associated protein 25 mutation induces immaturity of the dentate granule cells of adult mice. Mol Brain. 2013;6:12.
103. Hayashi Y, Nabeshima Y, Kobayashi K, Miyakawa T, Tanda K, Takao K, et al. Enhanced stability of hippocampal place representation caused by reduced magnesium block of NMDA receptors in the dentate gyrus. Hippocampus. 2014;7:44.
104. Crawley JN, Goodwin FK. Preliminary report of a simple animal behavior for the anxiolytic effects of benzodiazepines. Pharmacol Biochem Behav. 1980;13:167-70.
105. Takao K, Miyakawa T. Light/dark transition test for mice. J Vis Exp. 2006;1:104.
106. Komada M, Takao K, Miyakawa T. Elevated plus maze for mice. J Vis Exp. 2008;22:1088.
107. de Angelis L, File SE. Acute and chronic effects of three benzodiazepines in the social interaction anxiety test in mice. Psychopharmacology (Berl). 1979;64:127-9.
108. File SE. The use of social interaction as a method for detecting anxiolytic activity of chlordiazepoxide-like drugs. J Neurosci Methods. 1980;2:219-38.
109. Porsolt RD, Bertin A, Jalfre M. Behavioral despair in mice: a primary screening test for antidepressants. Arch Int Pharmacodyn Ther. 1977;229:327-36.
110. Ageta-Ishihara N, Yamakado H, Morita T, Hattori S, Takao K, Miyakawa T, et al. Chronic overload of SEPT4, a parkin substrate that aggregates in Parkinson's disease, causes behavioral alterations but not neurodegeneration in mice. Mol Brain. 2013;6:35.
111. Fujioka R, Nii T, Iwaki A, Shibata A, Ito I, Kitaichi K, et al. Comprehensive behavioral study of mGluR3 knockout mice: implication in schizophrenia related endophenotypes. Mol Brain. 2014;7:31.
112. Shoji H, Takao K, Hattori S, Miyakawa T. Contextual and cued fear conditioning test using a video analyzing system in mice. J Vis Exp. 2014;85:e50871.
113. Steru L, Chermat R, Thierry B, Simon P. The tail suspension test: a new method for screening antidepressants in mice. Psychopharmacology (Berl). 1985;85:367-70.
114. Onouchi T, Kobayashi K, Sakai K, Shimomura A, Smits R, Sumi-Ichinose C, et al. Targeted deletion of the C-terminus of the mouse adenomatous polyposis coli tumor suppressor results in neurologic phenotypes related to schizophrenia. Mol Brain. 2014;7:1-14.