Overview of current mouse models of autism and strategies for their development using CRISPR/Cas9 technology

Authors

  • Anja DOMADENIK University of Ljubljana, Biotechnical Faculty, Academic Study Programme in Biotechnology, Ljubljana, Slovenia

DOI:

https://doi.org/10.14720/aas.2018.112.1.3

Keywords:

medicine, autism, genetics, functional genomics, genetic engineering, CRISPR/Cas9, model organisms, Mus musculus, behavioural studies

Abstract

Autism spectrum disorders (ASD) are a group of highly heterogenous neurological disorders that are believed to have strong genetic component. Due to the limited use of approaches of functional genomics in human medicine, creating adequate animal models for the study of complex human diseases shows great potential. There are several already established mouse models of autism that offer insight into single phenotypic traits, although causes for its complex phenotype have not yet been fully understood. Development of new technologies, such as CRISPR/Cas9, represent great capability for targeted genome engineering and establishment of new animal models. This article provides an up to date overview of current knowledge in the area of autism genomics and describes the potential of CRISPR/Cas9 technology for the establishment of new mouse models, representing sgRNA design as one of the initial steps in planning a CRISPR/Cas9 single knock-out experiment. In addition, it offers an overview of current approaches to behavioural studies, explaining how relevant animal models could be developed.

References

Amir, R. E., Van den Veyver, I. B., Wan, M., Tran, C. Q., Francke, U., Zoghbi, H. Y. (1999). Rett syndrome is caused by mutations in X-linked MECP2, encoding methyl-CpG-binding protein 2. Nature Genetics, 23(2), 185–8. https://doi.org/10.1038/13810

Anders, C., Niewoehner, O., Duerst, A., Jinek, M. (2014). Structural basis of PAM-dependent target DNA recognition by the Cas9 endonuclease. Nature, 513(7519), 569–573. https://doi.org/10.1038/nature13579

Asperger, H. (1944). Die „Autistischen Psychopathen” im Kindesalter. Archiv für Psychiatrie und Nervenkrankheiten, 117(1), 76–136. https://doi.org/10.1007/BF01837709

Bailey, A., Le Couteur, A., Gottesman, I., Bolton, P., Simonoff, E., Yuzda, E., Rutter, M. (1995). Autism as a strongly genetic disorder: evidence from a British twin study. Psychological Medicine, 25(1), 63–77. https://doi.org/10.1017/S0033291700028099

Barrangou, R, Fremaux, C., Deveau, H., Richards, M., Boyaval, P., Moineau, S., ... Horvath, P. 2007. CRISPR Provides Acquired Resistance Against Viruses in Prokaryotes. Science, 315(5819), 1709. https://doi.org/10.1126/science.1138140

Barrangou, R., & Horvath, P. (2012). CRISPR: New Horizons in Phage Resistance and Strain Identification. Annual Review of Food Science and Technology, 3(1), 143–162. https://doi.org/10.1146/annurev-food-022811-101134

Benchling, Biology Software. (2017). https://benchling.com/ (06.01.2018)

Bey, A. L., & Jiang, Y. H. (2014). Overview of mouse models of autism spectrum disorders. Current Protocols in Pharmacology, 66, 5.66.1–26. https://doi.org/10.1002/0471141755.ph0566s66

Blundell, J., Blaiss, C. A., Etherton, M. R., Espinosa, F., Tabuchi, K., Walz, C., ... Powell, C. M. (2010). Neuroligin 1 deletion results in impaired spatial memory and increased repetitive behavior. The Journal of neuroscience : the official journal of the Society for Neuroscience, 30(6), 2115–2129. https://doi.org/10.1523/JNEUROSCI.4517-09.2010

Bolivar, V. J., Walters, S. R., Phoenix, J. L. (2007). Assessing Autism-like Behavior in Mice: Variations in Social Interactions Among Inbred Strains. Behavioural brain research, 176(1), 21–26. https://doi.org/10.1016/j.bbr.2006.09.007

Bolotin, A., Quinquis, B., Sorokin, A., Ehrlich, S. D. (2005). Clustered regularly interspaced short palindrome repeats (CRISPRs) have spacers of extrachromosomal origin. Microbiology, 151(Pt 8), 2551–61. https://doi.org/10.1099/mic.0.28048-0

Bressan, R. B., Dewari, P. S., Kalantzaki, M., Gangoso, E., Matjusaitis, M., Garcia-Diaz, C., ... Pollard, S. M. (2017). Efficient CRISPR/Cas9-assisted gene targeting enables rapid and precise genetic manipulation of mammalian neural stem cells. Development, 144(4), 635–648. https://doi.org/10.1242/dev.140855

Clifford, S., Dissanayake, C., Bui, Q. M., Huggins, R., Taylor, A. K., Loesch, D. Z. (2007). Autism spectrum phenotype in males and females with fragile X full mutation and premutation. Journal of Autism and Developmental Disorders, 37(4), 738–47. https://doi.org/10.1007/s10803-006-0205-z

Crawley, J. N. (2004). Designing mouse behavioral tasks relevant to autistic-like behaviors. Mental Retardation and Developmental Disability Research Reviews, 10(4), 248–58. https://doi.org/10.1002/mrdd.20039

Crawley, J. N., Chen, T., Puri, A., Washburn, R., Sullivan, T. L., Hill, J. M., ... Young, W. S. (2007). Social approach behaviors in oxytocin knockout mice: comparison of two independent lines tested in different laboratory environments. Neuropeptides, 41(3), 145–63. https://doi.org/10.1016/j.npep.2007.02.002

Deltcheva, E., Chylinski, K., Sharma, C. M., Gonzales, K., Chao, Y., Pirzada, Z. A., ... Charpentier, E. (2011). CRISPR RNA maturation by trans-encoded small RNA and host factor RNase III. Nature, 471(7340), 602–7. https://doi.org/10.1038/nature09886

Doench, J. G., Fusi, N., Sullender, M., Hegde, M., Vaimberg, E. W., Donovan, K. F., ... Root, D. E. (2016). Optimized sgRNA design to maximize activity and minimize off-target effects of CRISPR-Cas9. Nature Biotechnology, 34, 2, 184–191. https://doi.org/10.1038/nbt.3437

Domadenik, A. (2018). Genetsko ozadje avtizma in zasnova mišjega modela s tehnologijo CRISPR/Cas9 (Bachelor thesis). [A. Domadenik].

Doudna, J. A., Charpentier, E. (2014). Genome editing. The new frontier of genome engineering with CRISPR-Cas9. Science, 346(6213), 1258096. https://doi.org/10.1126/science.1258096

Fmr1 knockout mice: a model to study fragile X mental retardation. The Dutch-Belgian Fragile X Consortium. (1994). Cell, 78(1), 23–33.

Folstein, S., & Rutter, M. (1977). Infantile autism: a genetic study of 21 twin pairs. Journal of Child Psychology and Psychiatry, 18(4), 297–321. https://doi.org/10.1111/j.1469-7610.1977.tb00443.x

Fu, Y., Foden, J. A., Khayter, C., Maeder, M. L., Reyon, D., Joung, J. K., Sander, J. D. (2013). High frequency off-target mutagenesis induced by CRISPR-Cas nucleases in human cells. Nature biotechnology, 31(9), 822–826. https://doi.org/10.1038/nbt.2623

Gagnon, J. A., Valen, E., Thyme, S. B., Huang, P., Akhmetova, L., Pauli, A., ... Schier A. F. (2014). Efficient mutagenesis by Cas9 protein-mediated oligonucleotide insertion and large-scale assessment of single-guide RNAs. PLoS One, 9(5), e98186. https://doi.org/10.1371/journal.pone.0098186

Galef, B. G., Jr. (2003). Social learning of food preferences in rodents: rapid appetitive learning. Current Protocols in Neuroscience, Chapter 8, Unit 8.5D. https://doi.org/10.1002/0471142301.ns0805ds21

Gasiunas, G., Barrangou, R., Horvath, P., Siksnys ,V. (2012). Cas9-crRNA ribonucleoprotein complex mediates specific DNA cleavage for adaptive immunity in bacteria. Proceedings of the National Academy of Science U S A, 109(39), E2579–86. https://doi.org/10.1073/pnas.1208507109

Goorden, S. M., van Woerden, G. M. van der Weerd, L., Cheadle, J. P., Elgersma, Y. (2007). Cognitive deficits in Tsc1+/− mice in the absence of cerebral lesions and seizures. Annals of Neurology, 62(6), 648–55. https://doi.org/10.1002/ana.21317

Guilinger, J. P., Thompson, D. B., Liu ,D. R. (2014). Fusion of catalytically inactive Cas9 to FokI nuclease improves the specificity of genome modification. Nature Biotechnology, 32(6), 577–582. https://doi.org/10.1038/nbt.2909

Hai, T., Teng, F., Guo, R., Li, W., Zhou, Q. (2014). One-step generation of knockout pigs by zygote injection of CRISPR/Cas system. Cell Research, 24, 372–5. https://doi.org/10.1038/cr.2014.11

Hsu, P. D., Scott, D. A., Weinstein, J. A., Ran, F. A., Konermann, S., Agarwala, V., ... Zhang, F. (2013). DNA targeting specificity of RNA-guided Cas9 nucleases. Nature Biotechnology, 31(9), 827–32. https://doi.org/10.1038/nbt.2647

Ishino, Y., Shinagawa, H., Makino, K., Amemura, M., Nakata, A. (1987). Nucleotide sequence of the iap gene, responsible for alkaline phosphatase isozyme conversion in Escherichia coli, and identification of the gene product. Journal of Bacteriology, 169(12), 5429–5433. https://doi.org/10.1128/jb.169.12.5429-5433.1987

Jamain, S., Radyushkin, K., Hammerschmidt, K., Granon, S., Boretius, S., Varoqueaux, F., ... Brose, N. (2008). Reduced social interaction and ultrasonic communication in a mouse model of monogenic heritable autism. Proceedings of the National Academy of Sciences U S A, 105(5), 1710–5. https://doi.org/10.1073/pnas.0711555105

Jansen, R., Embden, J. D., Gaastra, W., Schouls, L. M. (2002). Identification of genes that are associated with DNA repeats in prokaryotes. Molecular Microbiology, 43(6), 1565–75. https://doi.org/10.1046/j.1365-2958.2002.02839.x

Jinek, M., Chylinski, K., Fonfara, I., Hauer, M., Doudna, J. A., Charpentier, E. (2012). A programmable dual-RNA-guided DNA endonuclease in adaptive bacterial immunity. Science, 337(6096), 816–21. https://doi.org/10.1126/science.1225829

Kalebic, N., Taverna, E., Tavano, S., Wong, F. K., Suchold, D., Winkler, S., ... Sarov, M. (2016). CRISPR/Cas9-induced disruption of gene expression in mouse embryonic brain and single neural stem cells in vivo. EMBO Reports, 17(3), 338–48. https://doi.org/10.15252/embr.201541715

Kanner, L. 1943. Autistic Disturbances of Affective Contact. Nervous Child: Journal of Psychopathology, Psychotherapy, Mental Hygiene and Guidance of the Child, 2, 217–250.

Kim, H. G., Kishikawa, S., Higgins, A. W., Seong, I. S., Donovan, D. J., Shen, Y., ... Gusella, J. F. (2008). Disruption of Neurexin 1 Associated with Autism Spectrum Disorder. American Journal of Human Genetics, 82(1), 199–207. https://doi.org/10.1016/j.ajhg.2007.09.011

Kim, Y. G., Cha, J., Chandrasegaran, S. 1996. Hybrid restriction enzymes: zinc finger fusions to Fok I cleavage domain. Proceedings of the National Academy of Sciences U S A, 93(3), 1156–60. https://doi.org/10.1073/pnas.93.3.1156

Kim, Y. S., Leventhal, B. L., Koh, Y. J., Fombonne, E., Laska, E., Lim, E. C., ... Grinker, R. R. (2011). Prevalence of autism spectrum disorders in a total population sample. American Journal of Psychiatry, 168(9), 904–12. https://doi.org/10.1176/appi.ajp.2011.10101532

Kinney, D. K., Munir, K. M., Crowley, D. J., Miller, A. M. (2008). Prenatal stress and risk for autism. Neuroscience and biobehavioral reviews, 32(8), 1519–1532. https://doi.org/10.1016/j.neubiorev.2008.06.004

Labun, K., Montague, T. G., Gagnon, J. A., Thyme, S. B., Valen, E. (2016). CHOPCHOP v2: a web tool for the next generation of CRISPR genome engineering. Nucleic Acids Research, 44(W1), W272–6. https://doi.org/10.1093/nar/gkw398

Lai, M. C., Lombardo, M. V., Pasco, G., Ruigrok, A. N., Wheelwright, S. J., Sadek, S. A., ... Baron-Cohen, S. (2011). A behavioral comparison of male and female adults with high functioning autism spectrum conditions. PLoS One, 6(6), e20835. https://doi.org/10.1371/journal.pone.0020835

Lin, Y., Cradick, T. J., Brown, M. T., Deshmukh, H., Ranjan, P., Sarode, N., ... Bao, G. (2014). CRISPR/Cas9 systems have off-target activity with insertions or deletions between target DNA and guide RNA sequences. Nucleic Acids Research, 42(11), 7473–7485. https://doi.org/10.1093/nar/gku402

Lionel, A. C., Tammimies, K., Vaags, A. K., Rosenfeld, J. A., Ahn, J. W., Merico, ... Scherer, S. W. (2014). Disruption of the ASTN2/TRIM32 locus at 9q33.1 is a risk factor in males for autism spectrum disorders, ADHD and other neurodevelopmental phenotypes. Human Molecular Genetics, 23(10), 2752–68. https://doi.org/10.1093/hmg/ddt669

Liu, D., Wang, Z., Xiao, A., Zhang, Y., Li, W., Zu, Y., ... Zhang, B. (2014). Efficient gene targeting in zebrafish mediated by a zebrafish-codon-optimized cas9 and evaluation of off-targeting effect. Journal of Genetics and Genomics, 41(1), 43–6. https://doi.org/10.1016/j.jgg.2013.11.004

Liu, X., Homma, A., Sayadi, J., Yang, S., Ohashi, J., Takumi, T. (2016). Sequence features associated with the cleavage efficiency of CRISPR/Cas9 system. Scientific Reports, 6, 19675. https://doi.org/10.1038/srep19675

Lyall, K., Schmidt, R. J., Hertz-Picciotto, I. (2014). Maternal lifestyle and environmental risk factors for autism spectrum disorders. International Journal of Epidemiology, 43(2), 443–464. https://doi.org/10.1093/ije/dyt282

Lynch, C. J., Uddin L. Q., Supekar K., Khouzam A., Phillips J., Menon V. 2013. Default mode network in childhood autism: posteromedial cortex heterogeneity and relationship with social deficits. Biological Psychiatry 74(3), 212–9. https://doi.org/10.1016/j.biopsych.2012.12.013

Makarova, K. S., Grishin, N. V., Shabalina, S. A., Wolf, Y. I., Koonin, E. V. (2006). A putative RNA-interference-based immune system in prokaryotes: computational analysis of the predicted enzymatic machinery, functional analogies with eukaryotic RNAi, and hypothetical mechanisms of action. Biology Direct, 1(7), 1–26. https://doi.org/10.1186/1745-6150-1-7

Marco, E. J., Skuse, D. H. (2006). Autism-lessons from the X chromosome. Social cognitive and affective neuroscience, 1(3), 183–193. https://doi.org/10.1093/scan/nsl028

McFarlane, H. G., Kusek, G. K., Yang, M., Phoenix, J. L., Bolivar, V. J., Crawley, J. N. (2008). Autism-like behavioral phenotypes in BTBR T+tf/J mice. Genes, Brain and Behaviour, 7(2), 152–63. https://doi.org/10.1111/j.1601-183X.2007.00330.x

Meta-analysis of GWAS of over 16,000 individuals with autism spectrum disorder highlights a novel locus at 10q24.32 and a significant overlap with schizophrenia. (2017). Molecular Autism, 8(21), 1–17. https://doi.org/10.1186/s13229-017-0137-9

Mojica, F. J., Diez-Villasenor, C., Garcia-Martinez, J., Soria, E. (2005). Intervening sequences of regularly spaced prokaryotic repeats derive from foreign genetic elements. Journal of Molecular Evolution, 60(2), 174–82. https://doi.org/10.1007/s00239-004-0046-3

Mojica, F. J., Diez-Villasenor, C., Soria, E., Juez, G. (2000). Biological significance of a family of regularly spaced repeats in the genomes of Archaea, Bacteria and mitochondria. Molecular Microbiology, 36(1), 244–6. https://doi.org/10.1046/j.1365-2958.2000.01838.x

Molina, J., Carmona-Mora, P., Chrast, J., Krall, P. M., Canales, C. P., Lupski, ... Walz, K. (2008). Abnormal social behaviors and altered gene expression rates in a mouse model for Potocki-Lupski syndrome. Human Molecular Genetics, 17(16), 2486–95. https://doi.org/10.1093/hmg/ddn148

Montague, T. G., Cruz, J. M., Gagnon, J. A., Church, G. M., Valen, E. (2014). CHOPCHOP: a CRISPR/Cas9 and TALEN web tool for genome editing. Nucleic Acids Research, 42(Web Server issue), W401–7. https://doi.org/10.1093/nar/gku410

Moretti, P., Bouwknecht, J. A., Teague, R., Paylor, R., Zoghbi, H. Y. (2005). Abnormalities of social interactions and home-cage behavior in a mouse model of Rett syndrome. Human Molecular Genetics, 14(2), 205–20. https://doi.org/10.1093/hmg/ddi016

Mottron, L., Duret, P., Mueller, S., Moore, R. D., Forgeot d‘Arc, B., Jacquemont, S., Xiong, L. (2015). Sex differences in brain plasticity: a new hypothesis for sex ratio bias in autism. Molecular Autism, 6(33), 1–19. https://doi.org/10.1186/s13229-015-0024-1

Moy, S. S., Nadler, J. J., Perez, A., Barbaro, R. P., Johns, J. M., Magnuson, T. R., ... Crawley, J. N. (2004). Sociability and preference for social novelty in five inbred strains: an approach to assess autistic-like behavior in mice. Genes, Brain and Behaviour, 3(5), 287–302. https://doi.org/10.1111/j.1601-1848.2004.00076.x

Moy, S. S., Nadler, J. J., Young, N. B., Perez, A., Holloway, L. P., Barbaro, R. P., ... Crawley, J. N. (2007). Mouse behavioral tasks relevant to autism: phenotypes of 10 inbred strains. Behavioural Brain Research, 176(1), 4–20. https://doi.org/10.1016/j.bbr.2006.07.030

Moy, S. S., Nadler, J. J., Poe, M. D., Nonneman, R. J., Young, N. B., Koller, B. H., ... Bodfish, J. W. (2008). Development of a Mouse Test for Repetitive, Restricted Behaviors: Relevance to Autism. Behavioural brain research, 188(1), 178–194. https://doi.org/10.1016/j.bbr.2007.10.029

Peters, S. U., Beaudet, A. L., Madduri, N., Bacino, C. A. (2004). Autism in Angelman syndrome: implications for autism research. Clinical Genetics, 66(6), 530–6. https://doi.org/10.1111/j.1399-0004.2004.00362.x

Piek, J. P., & Dyck, M. J. (2004). Sensory-motor deficits in children with developmental coordination disorder, attention deficit hyperactivity disorder and autistic disorder. Human Movement Science, 23(3–4), 475–88. https://doi.org/10.1016/j.humov.2004.08.019

Ran, F. A., Hsu, P. D., Lin, C. Y., Gootenberg, J. S., Konermann, S., Trevino, A. E., ... Zhang, F. (2013). Double nicking by RNA-guided CRISPR Cas9 for enhanced genome editing specificity. Cell, 154(6), 1380–9. https://doi.org/10.1016/j.cell.2013.08.021

Ren, X., Sun, J., Housden, B. E., Hu, Y., Roesel, C., Lin, S., ... Ni, J. Q. (2013). Optimized gene editing technology for Drosophila melanogaster using germ line-specific Cas9. Proceedings of the National Academy of Sciences U S A, 110(47), 19012–7. https://doi.org/10.1073/pnas.1318481110

Romanienko, P. J., Giacalone, J., Ingenito, J., Wang, Y., Isaka, M., Johnson, T., ... Mark, W. H. (2016). A Vector with a Single Promoter for In Vitro Transcription and Mammalian Cell Expression of CRISPR gRNAs. PLoS ONE 11(2), e0148362. https://doi.org/10.1371/journal.pone.0148362

Rubenstein, J. L., & Merzenich, M. M. (2003). Model of autism: increased ratio of excitation/inhibition in key neural systems. Genes, Brain and Behaviour, 2(5), 255–67. https://doi.org/10.1034/j.1601-183X.2003.00037.x

Rudin, N., Sugarman, E., Haber, J. E. (1989). Genetic and Physical Analysis of Double-Strand Break Repair and Recombination in Saccharomyces Cerevisiae. Genetics, 122(3), 519–534.

Scearce-Levie, K., Roberson, E. D., Gerstein, H., Cholfin, J. A., Mandiyan, V. S., Shah, N. M., ... Mucke, L. (2008). Abnormal social behaviors in mice lacking Fgf17. Genes, Brain and Behaviour, 7(3), 344–54. https://doi.org/10.1111/j.1601-183X.2007.00357.x

Schaefer, G. B., & Mendelsohn, N. J. (2013). Clinical genetics evaluation in identifying the etiology of autism spectrum disorders: 2013 guideline revisions. Genetics in Medicine, 15(5), 399–407. https://doi.org/10.1038/gim.2013.32

Shen B., Zhang, W., Zhang, J., Zhou, J., Wang, J., Chen, L., ... Skarnes W. C. (2014). Efficient genome modification by CRISPR-Cas9 nickase with minimal off-target effects. Nature Methods, 11(4), 399–402. https://doi.org/10.1038/nmeth.2857

Silverman, J. L., Yang, M., Lord, C., Crawley, J. N. (2010). Behavioural phenotyping assays for mouse models of autism. Nature Reviews Neuroscience, 11(7), 490–502. https://doi.org/10.1038/nrn2851

Sorek, R., Kunin, V., Hugenholtz, P. (2008). CRISPR--a widespread system that provides acquired resistance against phages in bacteria and archaea. Nature Reviews Microbiology, 6(3), 181–6. https://doi.org/10.1038/nrmicro1793

Steffenburg, S., Gillberg, C., Hellgren, L., Andersson, L., Gillberg, I. C., Jakobsson, G., Bohman, M. (1989). A twin study of autism in Denmark, Finland, Iceland, Norway and Sweden. Journal of Child Psychology and Psychiatry, 30(3), 405–16. https://doi.org/10.1111/j.1469-7610.1989.tb00254.x

Supekar, K., Uddin, L. Q., Khouzam, A., Phillips, J., Gaillard, W. D., Kenworthy, L. E., ... Menon, V. (2013). Brain hyperconnectivity in children with autism and its links to social deficits. Cell Reports, 5(3), 738–47. https://doi.org/10.1016/j.celrep.2013.10.001

Tang, T. H., Bachellerie, J. P., Rozhdestvensky, T., Bortolin, M. L., Huber, H., Drungowski, M., ... Huttenhofer, A. (2002). Identification of 86 candidates for small non-messenger RNAs from the archaeon Archaeoglobus fulgidus. Proceedings of the National Academy of Sciences U S A, 99(11), 7536–41. https://doi.org/10.1073/pnas.112047299

Tsai, S. Q., Wyvekens, N., Khayter, C., Foden, J. A., Thapar, V., Reyon, D., ... Joung, J. K. (2014). Dimeric CRISPR RNA-guided FokI nucleases for highly specific genome editing. Nature Biotechnology, 32(6), 569–76. https://doi.org/10.1038/nbt.2908

Uddin, L. Q., Supekar, K., Menon, V. (2013). Reconceptualizing functional brain connectivity in autism from a developmental perspective. Frontiers in Human Neuroscience, 7(article 458), 1–11. https://doi.org/10.3389/fnhum.2013.00458

Vattikuti, S., & Chow, C. C. (2010). A computational model for cerebral cortical dysfunction in autism spectrum disorders. Biological Psychiatry, 67(7), 672–8. https://doi.org/10.1016/j.biopsych.2009.09.008

Vorstman, J. A. S., Parr, J. R., Moreno-De-Luca, D., Anney, R. J. L., Nurnberger, J. I., Jr., Hallmayer, J. F. (2017). Autism genetics: opportunities and challenges for clinical translation. Nature Reviews Genetics, 18(6), 362–376. https://doi.org/10.1038/nrg.2017.4

Vouillot, L., Thélie, A., Pollet, N. (2015). Comparison of T7E1 and Surveyor Mismatch Cleavage Assays to Detect Mutations Triggered by Engineered Nucleases. G3: Genes|Genomes|Genetics, 5(3), 407–415. https://doi.org/10.1534/g3.114.015834

Wettstein, R., Bodak, M., Ciaudo, C. (2016). Generation of a Knockout Mouse Embryonic Stem Cell Line Using a Paired CRISPR/Cas9 Genome Engineering Tool. Methods in Molecular Biology, 1341, 321–43. https://doi.org/10.1007/7651_2015_213

Wilson, P. M., Fryer, R. H., Fang, Y., Hatten, M. E. (2010). Astn2, A Novel Member of the Astrotactin Gene Family, Regulates the Trafficking of ASTN1 During Glial-Guided Neuronal Migration. The Journal of neuroscience : the official journal of the Society for Neuroscience, 30(25), 8529–8540. https://doi.org/10.1523/JNEUROSCI.0032-10.2010

Wing, L. (1981). Sex ratios in early childhood autism and related conditions. Psychiatry Research, 5(2), 129–37. https://doi.org/10.1016/0165-1781(81)90043-3

Wohr, M., Roullet, F. I., Crawley, J. N. (2011). Reduced scent marking and ultrasonic vocalizations in the BTBR T+tf/J mouse model of autism. Genes, Brain and Behaviour, 10(1), 35–43. https://doi.org/10.1111/j.1601-183X.2010.00582.x

Wrenn, C. C. (2004). Social transmission of food preference in mice. Current Protocols in Neuroscience, 28(1), 8.5G.1–8.5G.7. https://doi.org/10.1002/0471142301.ns0805gs28

Wu, X., Kriz, A. J., Sharp, P. A. (2014). Target specificity of the CRISPR-Cas9 system. Quantitative biology, 2(2), 59–70. https://doi.org/10.1007/s40484-014-0030-x

Yang, H., Wang, H., Jaenisch, R. (2014). Generating genetically modified mice using CRISPR/Cas-mediated genome engineering. Nature Protocols, 9(8), 1956–68. https://doi.org/10.1038/nprot.2014.134

Yang, M., Clarke, A. M., Crawley, J. N. (2009). Postnatal lesion evidence against a primary role for the corpus callosum in mouse sociability. European Journal of Neuroscience, 29(8), 1663–77. https://doi.org/10.1111/j.1460-9568.2009.06714.x

Yang, M., & Crawley, J. N. (2009). Simple behavioral assessment of mouse olfaction. Current Protocols in Neuroscience, 48(1), 8.24.1–8.24.12. https://doi.org/10.1002/0471142301.ns0824s48

Yin, J., & Schaaf, C. P. (2017). Autism genetics – an overview. Prenatal Diagnostics, 37(1), 14–30. https://doi.org/10.1002/pd.4942

Yuen, C. R. K. , Merico, D., Bookman, M., Howe, L. J, Thiruvahindrapuram, B., Patel, R. V., ... Scherer, S. W. (2017). Whole genome sequencing resource identifies 18 new candidate genes for autism spectrum disorder. Nature Neuroscience, 20(4), 602–611. https://doi.org/10.1038/nn.4524

Zhang Lab, MIT. (2013). Optimized CRISPR Design. Retrieved from http://crispr.mit.edu/ (06.01.2018)

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30. 09. 2018

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DOMADENIK, A. (2018). Overview of current mouse models of autism and strategies for their development using CRISPR/Cas9 technology. Acta Agriculturae Slovenica, 112(1), 19–30. https://doi.org/10.14720/aas.2018.112.1.3

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