BTBR T~(+)tf/J Mouse: An Ideal Animal Model for Autism Spectrum Disorders
Abstract: Autism spectrum disorder (ASD) is a complex heterogeneous of neuro developmental disorders which originate from the early childhood with the core symptoms of impaired communication, social impairments, and restricted and repetitive behaviors and interests. Research has so far indicated that ASD exists genetic basis and may be induced bursting out under certain conditions which include the factors such as maternal immunity, autoimmune disorder, natural environment etc., and children with ASD exist cerebral dysplasia. However, the pathogenesis of ASD is still inadequately understood which needs us to make further study on it. Animal model can be used as an important basis for evaluating the experimental results. Therefore, to establish an appropriate ASD model is the foundation of experiment. Since ASD is a kind of disease caused by many factors and may include many kinds of pathogenetic mechanisms, whe- ther we can choose an animal model which can accurately replicate the pathological and clinical features of ASD is of great significance for the further research of ASD. BTBR T~(+)tf/J (BTBR for short) mice is a kind of inbred strain mice which not only possesses the core symptoms such as reduction of social intercourse, lack of ultrasonic on social occasions and severe repeated grooming behavior, but also possesses cerebral dysplasia and immune biochemical index abnormalities similar to ASD. Based on this, BTBR mice is currently the ideal model for the study of autism. The aim of this article is to summarize the relationship between BTBR mice and ASD.
文章引用: 王 冰 , 杜 琳 , 单 玲 , 李洪华 , 冯俊燕 , 贾飞勇 (2014) BTBR T~(+)tf/J小鼠：孤独症谱系障碍理想的动物模型。 国际神经精神科学杂志， 3， 13-19. doi: 10.12677/IJPN.2014.33003
 Silverman, J.L., Yang, M., Lord, C. and Crawley, J.N. (2010) Behavioural phenotyping assays for mouse models of autism. Nature Reviews Neuroscience, 11, 490-502.
 Crawley, J.N. (2012) Translational animal models of autism and neurodevelopmental disorders. Clinical Research, 14, 293-305.
 Lord, C., Petkova, E., Hus, V., et al. (2012) A multisite study of the clinical diagnosis of different autism spectrum disorders. Archives of General Psychiatry, 69, 306-313.
 Yang, M., Scattoni, M.L., Zhodzishsky, V., Chen, T., Caldwell, H., Young, W.S., McFarlane, H.G. and Crawley, J.N. (2007) Social approach behaviors are similar on conventional versus reverse lighting cycles, and in replications across cohorts, in BTBR T+ tf/J, C57BL/6J, and vasopressin receptor 1B mutant mice. Frontiers in Behavioral Neuroscience, 1, 1.
 Bolivara, V.J., Waltersa, S.R. and Phoenix, J.L. (2007) Assessing autism-like behavior in mice: Variations in social interactions among inbred strains. Behavioural Brain Research, 176, 21-26.
 Moy, S.S., Nadler, J.J., Young, N.B., Perez, A., Holloway, L.P., Barbaro, R.P., et al. (2007) Mouse behavioral tasks re- levant to autism: Phenotypes of ten inbred strains. Behavioural Brain Research, 176, 4-20.
 Yang, M., Silverman, J.L. and Crawley, J.N. (2011) Au-tomated three-chambered social approach task for mice. Current Protocols in Neuroscience.
 McFarlane, H.G., Kusek, G.K., Yang, M., Phoenix, J.L., Bolivar, V.J. and Crawley, J.N. (2008) Autism-like behavioral phenotypes in BTBR T+tf/J mice. Genes, Brain and Behavior, 7, 152-163.
 Brodkin, E.S. (2007) BALB/c mice: Low sociability and other phenotypes that be relevant to autism. Behavioural Brain Research, 176, 53-65.
 Pobbe, R.L., Defensor, E.B., Pearson, B.L., Bolivar, V.J., Blanchard, D.C. and Blanchard, R.J. (2011) General and social anxiety in the BTBR T+tf/J mouse strain. Behavioural Brain Research, 216, 446-451.
 Ryan, B.C., Young, N.B., Moy, S.S. and Crawley, J.N. (2008) Olfactory cues are sufficient to elicit social approach behaviors but not social transmission of food preference in C57BL/6J mice. Behavioural Brain Research, 193, 235- 242.
 Yang, M. and Crawley, J.N. (2009) Simple behavioral assessment of mouse olfaction. Current Protocols in Neuroscience.
 Wöhr, M., Roullet, F.I. and Crawley, J.N. (2011) Reduced scent marking and ultrasonic vocalizations in the BTBR T+tf/J mouse model of autism. Genes, Brain and Behavior, 10, 35-43.
 Yang, M., Loureiro, D., Kalikhman, D. and Crawley, J.N. (2013) Male mice emit distinct ultrasonic vocalizations when the female leaves the social interaction arena. Frontiers in Behavioral Neuroscience, 7, 159.
 Pearson, B.L., Pobbe, R.L.H., Defensor, E.B., Oasay, L., Bolivar, V.J., Blanchard, D.C., et al. (2011) Motor and cognitive stereotypies in the BTBR T+tf/J mouse model of autism. Genes, Brain and Behavior, 10, 228-235.
 Silva, A.J. and Ehninger, D. (2009) Adult reversal of cognitive phenotypes in neurodevelopmental disorders. Journal of Neurodevelopmental Disorders, 1, 150-157.
 Yang, M., Clarke, A.M. and Crawley, J.N. (2009) Postnatal lesion evidence against a primary role for the corpus callosum in mouse sociability. European Journal of Neuroscience, 29, 1663-1677.
 Yang, M., Perry, K., Weber, M.D., Katz, A.M. and Crawley, J.N. (2011) Social peers rescue aut-ism-relevant sociability deficits in adolescent mice. Autism Research, 4, 17-27.
 Moy, S.S., Nadler, J.J., Poe, M.D., Nonneman, R.J., Young, N.B., Koller, B.H., et al. (2008) Development of a mouse test for repetitive, restricted behaviors: Relevance to autism. Behavioural Brain Research, 188, 178-194.
 Amodeo, D.A., Jones, J.H., Sweeney, J.A. and Ragozzino, M.E. (2012) Differences in BTBR T+tf/J and C57BL/6J mice on probabilistic reversal learning and stereotyped behaviors. Behavioural Brain Research, 227, 64-72.
 Langen, M., Schnack, H.G., Nederveen, H., Bos, D., Lahuis, B.E., de Jonge, M.V., van Engeland, H. and Durston, S. (2009) Changes in the developmental trajectories of striatum in autism. Biological Psychiatry, 66, 327-333.
 Frazier, T.W. and Hardan, A.Y. (2009) A meta-analysis of the corpus callosum in autism. Biological Psychiatry, 66, 935-941.
 Casanova, M.F., El-Baz, A., Elnakib, A., Switala, A.E., Williams, E.L., Williams, D.L., Minshew, N.J. and Conturo, T.E. (2011) Quantitative analysis of the shape of the corpus callosum in patients with autism and comparison individuals. Autism, 15, 223-238.
 Wahlsten, D., Metten, P. and Crabbe, J.C. (2003) Survey of 21 inbred mouse strains in two laboratories reveals that BTBR T/+tf/tf has severely reduced hippocampal commissure and absent corpus callosum. Brain Research, 971, 47- 54.
 Shevelev, O.B., Rykova, V.I., Fedoseeva, L.A., Leberfarb, E.Y., Dymshits, G.M. and Kolosova, N.G. (2012) Expression of Ext1, Ext2, and heparanase genes in brain of senescence-accelerated OXYS rats in early ontogenesis and during development of neurodegenerative changes. Biochemistry (Moscow), 77, 56-61.
 Pearson, B.L., Corley, M.J., Vasconcellos, A., Blanchard, D.C. and Blanchard, R.J. (2013) Heparan sulfate deficiency in autistic postmortem brain tissue from the subventricular zone of the lateral ventricles. Behavioural Brain Research, 243, 138-145.
 Irie, F., Badie-Mahdavi, H. and Yamaguchi, Y. (2012) Autism-like socio-communicative deficits and stereotypies in mice lacking heparan sulfate. Proceedings of the National Academy of Sciences of the United States of America, 109, 5052-5056.
 Li, H., Yamagata, T., Mori, M. and Momoi, M.Y. (2002) Association of autism in two patients with hereditary multiple exostoses caused by novel deletion mutations of EXT1. Journal of Human Genetics, 47, 262-265.
 Karus, M., Samtleben, S., Busse, C., Tsai, T., Dietzel, I.D., Faissner, A., et al. (2012) Normal sulfation levels regulate spinal cord neural precursor cell proliferation and differentiation. Neural Development, 7, 20.
 Suzuki, K., Sugihara, G., Ouchi, Y., Nakamura, K., Tsujii, M., Futatsubashi, M., et al. (2011) Reduced acetylcholinesterase activity in the fusiform gyrus in adults with autism spectrum disorders. Archives of General Psychiatry, 68, 306- 313.
 McTighe, S.M., Neal, S.J., Lin, Q., Hughes, Z.A. and Smith, D.G. (2013) The BTBR mouse model of autism spectrum disorders has learning and attentional impairments and alterations in acetylcholine and kynurenic acid in prefrontal cor- tex. PLoS ONE, 8, e62189.
 Abdallah, M.W., Larsen, N., Grove, J., Norgaard-Pedersen, B., Thorsen, P., Mortensen, E.L., et al. (2012) Amniotic fluid chemokines and autism spectrum disorders: An exploratory study utilizing a Danish historic birth cohort. Brain, Behavior, and Immunity, 26, 170-176.
 Goines, P.E., Croen, L.A., Braunschweig, D., Yoshida, C.K., Grether, J., Hansen, R., et al. (2011) Increased midgestational IFN-γ, IL-4 and IL-5 in women bearing a child with autism: A case-control study. Molecular Autism, 2, 13.
 Rosenberg, R.E., Law, J.K., Yenokyan, G., McGready, J., Kaufmann, W.E. and Law, P.A. (2009) Characteristics and concordance of autism spectrum disorders among 277 twin pairs. Archives of Pediatrics & Adolescent Medicine, 163, 907-914.
 Hallmayer, J., Cleveland, S., Torres, A., Phillips, J., Cohen, B., Torigoe, T., et al. (2011) Genetic heritability and shared environmental factors among twin pairs with autism. Archives of General Psychiatry, 68, 1095-1102.
 Schwartzer, J.J., Careaga, M., Onore, C.E., Rushakoff, J.A., Berman, R.F. and Ashwood, P. (2013) Maternal immune activation and strain specific interactions in the development of autism-like behaviors in mice. Translational Psychiatry, 3, e240.
 Ashwood, P., Wills, S. and Van de Water, J. (2006) The immune response in autism: A new frontier for autism research. Journal of Leukocyte Biology, 80, 1-15.
 Vargas, D.L., Nascimbene, C., Krishnan, C., Zimmerman, A.W. and Pardo, C.A. (2005) Neuroglial activation and neu- roinflammation in the brain of patients with autism. Annals of Neurology, 57, 67-81.
 Li, X., Chauhan, A., Sheikh, A.M., Patil, S., Chauhan, V., Li, X.M., et al. (2009) Elevated immune response in the brain of autistic patients. Journal of Neuroimmunology, 207, 111-116.
 Morgan, J.T., Chana, G., Pardo, C.A., Achim, C., Semendeferi, K., Buckwalter, J., et al. (2010) Microglial activation and increased microglial density observed in the dorsolateral prefrontal cortex in autism. Biological Psychiatry, 68, 368-376.
 Ashwood, P., Krakowiak, P., Hertz-Picciotto, I., Hansen, R., Pessah, I. and Van de Water, J. (2011) Elevated plasma cytokines in autism spectrum disorders provide evidence of immune dysfunction and are associated with impaired behavioral out come. Brain, Behavior, and Immunity, 25, 40-45.
 Sweeten, T.L., Posey, D.J. and McDougle, C.J. (2003) High blood monocyte counts and neopterin levels in children with autistic disorder. The American Journal of Psychiatry, 160, 1691-1693.
 Jyonouchi, H., Geng, L., Cushing-Ruby, A. and Quraishi, H. (2008) Impact of innate immunity alinasubset of children with autism spectrum disorders: A case control study. Journal of Neuroinflammation 5, 52.
 Enstrom, A.M., Onore, C.E., Van de Water, J.A. and Ashwood, P. (2010) Differential monocyte responses to TLR ligands in children with autism spectrum disorders. Brain, Behavior, and Immunity, 24, 64-71.
 Onore, C.E., Careaga, M., Babineau, B.A., Schwartzer, J.J., Berman, R.F. and Ashwood, P. (2013) Inflammatory macrophage phenotype in BTBR Ttf/J mice. Frontiers in Neuroscience, 7, 158.
 Zou, H., Yu, Y., Sheikh, A.M., Malik, M., Yang, K., Wen, G., et al. (2011) Association of up regulated Ras/Raf/ ERK1/2 signaling with autism. Genes, Brain and Behavior, 10, 615-624.
 Pobbe, R.L., Pearson, B.L., Defensor, E.B., Bolivar, V.J., Blanchard, D.C. and Blanchard, R.J. (2010) Expression of social behaviors of C57BL/6J versus BTBR inbred mouse strains in the visible burrow system. Behavioural Brain Research, 214, 443-449.