kurskvestЧеловек и его здоровьеHumans and their health1998-57461998-5754Kursk State Medical University10.21626/vestnik/2022-4/08kurskvest-1106Research ArticleМЕДИКО-БИОЛОГИЧЕСКИЕ НАУКИMEDICOBIOLOGICAL SCIENCESПоведенческие аномалии в генетической модели миодистрофии Дюшенна у мышейBehavioral abnormalities in a genetic model of Duchenne myodystrophy in micehttps://orcid.org/0000-0001-9706-0699СолдатовВладислав ОлеговичSoldatovVladislav O.

канд. мед. наук, науч. сотрудник Лаборатории геномного редактирования в биомедицине и ветеринарии, НИУ БелГУ, г. Белгород

Cand. Sci. (Med.), Researcher at the Laboratory of Genomic Editing in Biomedicine and Veterinary Medicine, NRU BelGU, Belgorod, Russian Federation

pharmsoldatov@gmail.comhttps://orcid.org/0000-0001-9440-5866КарагодинаАнастасия ЮрьевнаKaragodinaAnastasia Yu.

мл. науч. сотрудник НИИ фармакологии живых систем, НИУ БелГУ, г. Белгород

junior researcher at the Research Institute of Pharmacology of Living Systems, NRU BelGU, Belgorod, Russian Federation

anastasiavolmedic@gmail.comhttps://orcid.org/0000-0002-8415-4562ПатрахановЕвгений АлександровичPatrakhanovEvgeny A.

мл. науч.сотрудник НИИ фармакологии живых систем, НИУ БелГУ, г. Белгород

junior researcher at the Research Institute of Pharmacology of Living Systems, NRU BelGU, Belgorod, Russian Federation

pateval7@gmail.comhttps://orcid.org/0000-0003-3138-2075ПокровскийВладимир МихайловичPokrovskyVladimir M.

мл. науч.сотрудник НИИ фармакологии живых систем, НИУ БелГУ, г. Белгород

junior researcher at the Research Institute of Pharmacology of Living Systems, NRU BelGU, Belgorod, Russian Federation

vmpokrovsky@yandex.ruhttps://orcid.org/0000-0002-7657-0937ПученковаОлеся АндреевнаPuchenkovaOlesya A.

мл. науч. сотрудник НИИ фармакологии живых систем, НИУ БелГУ, г. Белгород

junior researcher, Research Institute of Pharmacology of Living Systems, NRU BelGU, Belgorod, Russian Federation

lesya759@yandex.ruhttps://orcid.org/0000-0001-9737-6378БелашоваАнастасия ВладимировнаBelashovaAnastasia V.

студент, НИУ БелГУ, г. Белгород

student, NRU BelGU, Belgorod, Russian Federation

belashova_av@mail.ruhttps://orcid.org/0000-0002-3346-3242ЕгороваТатьяна ВладимировнаEgorovaTatyana V.

науч. сотрудник лаборатории моделирования и терапии наследственных заболеваний, ИБГ РАН, г. Москва

researcher at the Laboratory for Modeling and Therapy of Hereditary Diseases, IGB RAS, Moscow, Russian Federation

egorovatv@genebiology.ruhttps://orcid.org/0000-0001-9442-8371ПоликарповаАнна ВадимовнаPolikarpovaAnna V.

канд. биол. наук, науч. сотрудник лаборатории моделирования и терапии наследственных заболеваний, ИБГ РАН, г. Москва

Cand. Sci. (Biol.), Researcher at the Laboratory for Modeling and Therapy of Hereditary Diseases, IGB RAS, Moscow, Russian Federation

a.polikarpova.marlin@gmail.comhttps://orcid.org/0000-0001-9960-0863ДейкинАлексей ВасильевичDeikinAleksey V.

канд. биол. наук, доцент, директор «Объединенный центр генетических технологий», НИУ БелГУ, г. Белгород

Cand. Sci. (Biol.), Associate Professor, Director of the United Center for Genetic Technologies, NRU BelGU, Belgorod, Russian Federation

deykin@bsu.edu.ruhttps://orcid.org/0000-0002-2761-6249ПокровскийМихаил ВладимировичPokrovskyMikhail V.

д-р мед. наук, профессор кафедры фармакологии и клинической фармакологии, руководитель НИИ фармакологии живых систем, НИУ БелГУ, г. Белгород

Dr.. Sci. (Biol.), Professor of the Department of Pharmacology and Clinical Pharmacology, Head of the Research Institute of Pharmacology of Living Systems, NRU BelGU, Belgorod, Russian Federation

mpokrovsky@yandex.ruБелгородский государственный национальный исследовательский университет (НИУ БелГУ)РоссияBelgorod State National Research University (NRU BelGU)Russian FederationИнститут биологии гена РАН (ИБГ РАН)РоссияInstitute of Gene Biology of Russian Academy of Sciences (IGB RAS)Russian Federation2022301220222546372Copyright © Солдатов В.О., Карагодина А.Ю., Патраханов Е.А., Покровский В.М., Пученкова О.А., Белашова А.В., Егорова Т.В., Поликарпова А.В., Дейкин А.В., Покровский М.В., 20232023Солдатов В.О., Карагодина А.Ю., Патраханов Е.А., Покровский В.М., Пученкова О.А., Белашова А.В., Егорова Т.В., Поликарпова А.В., Дейкин А.В., Покровский М.В.Soldatov V.O., Karagodina A.Y., Patrakhanov E.A., Pokrovsky V.M., Puchenkova O.A., Belashova A.V., Egorova T.V., Polikarpova A.V., Deikin A.V., Pokrovsky M.V.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.kursk-vestnik.ru/jour/article/view/1106

Мутации гена Dmd , кодирующего мембранный белок дистрофин, ассоциированы с развитием тяжелых X-сцепленных мышечными заболеваниями - миодистрофии Дюшенна и Беккера. При этом наряду с классическими симптомами со стороны поперечнополосатой мускулатуры мутации дистрофина могут приводить к снижению когнитивных функций и поведенческим аномалиям. Цель: проведение пилотного анализа поведенческих и когнитивных особенностей у мышей с генетическим дефектом, воспроизводящим фенотип миодистрофии Дюшенна. Материалы и методы. Для оценки особенностей моторных функций и поведения мыши DmdDel8-34 (n=13) и контрольные животные дикого типа (n=12) были подвергнуты исследованию в тестах «Удержание груза», «Ротарод», «Приподнятый крестообразный лабиринт» и «Распознавание объектов». Результаты. Было обнаружено, что мыши, несущие мутацию DmdDel8-34 характеризуются снижением моторных функций, демонстрируют признаки тревожности, а также проявляют низкую исследовательскую активность. Обнаруженные особенности когнитивного и эмоционального статуса совпадают с клиническими наблюдениями, свидетельствующими о повышенном риске развития у пациентов с мутациями гена Dmd расстройств аутистического спектра и обсессивно-компульсивного расстройства. Таким образом было доказано, что с 8 недели жизни мыши линии DmdDel8-34 демонстрируют снижение показателей в тестах «Ротарод» и «Удержание груза». Поведенческое тестирование в тесте «Приподнятый крестообразный лабиринт» выявило снижение времени, достигающее статистически достоверной разницы в сравнении с контролем дикого типа на 12й неделе и при оценке когнитивных функций в тесте «Распознавание объектов» было показано, что мыши DmdDel8-34 демонстрируют увеличение значения индекса дискриминации, что является признаком увеличения эффективности гиппокампальной памяти. Заключение. Проведенное исследование позволило выявить некоторые поведенческие аномалии у генетически-модифицированных мышей, несущих крупную делецию экзонов 8-34 гена Dmd , кодирующего дистрофин.

Mutations in the Dmd gene encoding the membrane protein dystrophin are associated with the development of severe X-linked muscle diseases Duchenne and Becker myodystrophy. At the same time, along with the classic symptoms of striated muscles, dystrophin mutations can lead to a decrease in cognitive functions and behavioral abnormalities. Objective: conducting a pilot analysis of behavioral and cognitive characteristics in mice with a genetic defect that reproduces the phenotype of Duchenne myodystrophy. Materials and methods. To assess the features of motor functions and behavior, DmdDel8-34(n=13) and control animals of the wild type (n=12) were subjected to research in the tests "Load retention", "Rotarod", "Elevated plus maze" and "Object recognition". Results. It was found that mice carrying the DmdDel8-34 mutation are characterized by a decrease in motor functions, show signs of anxiety, and also show low exploratory activity. The detected features of the cognitive and emotional status are consistent with clinical observations indicating an increased risk of developing autism spectrum disorders and obsessive-compulsive disorder in patients with Dmd gene mutations. Thus, it was proved that from the 8th week of life, mice of the DmdDel8-34 line show a decrease in performance in the Rotarod and Load Retention tests. Behavioral testing in the Elevated Plus Maze test revealed a decrease in time reaching a statistically significant difference compared to the wild-type control at week 12, and when assessing cognitive functions in the Object Recognition test, it was shown that DmdDel8-34mice show an increase in the discrimination index value, which is a sign of increased efficiency of hippocampal memory. Conclusion. The study made it possible to identify some behavioral anomalies in genetically modified mice carrying a large deletion of exons 8-34 of the Dmd gene encoding dystrophin.

трансгенезмиодистрофия Дюшеннаповеденческие тестымоторные нарушенияtransgenesisDuchenne myodystrophybehavioral testsmotor disordersReferencesTerry E.E., Zhang X., Hoffmann C., Hughes L.D., Lewis S.A., Li J., Wallace M.J., Riley L.A., et al. Transcriptional profiling reveals extraordinary diversity among skeletal muscle tissues. Elife. 2018;7:e34613. DOI: 10.7554/eLife.34613.Terry E.E., Zhang X., Hoffmann C., Hughes L.D., Lewis S.A., Li J., Wallace M.J., Riley L.A., et al. Transcriptional profiling reveals extraordinary diversity among skeletal muscle tissues. Elife. 2018;7:e34613. DOI: 10.7554/eLife.34613.Frontera W.R., Ochala J. Skeletal muscle: a brief review of structure and function. Calcif Tissue Int. 2015;96(3):183-195. DOI: 10.1007/s00223-014-9915-y.Frontera W.R., Ochala J. Skeletal muscle: a brief review of structure and function. Calcif Tissue Int. 2015;96(3):183-195. DOI: 10.1007/s00223-014-9915-y.Colson B.A., Gruber S.J., Thomas D.D. Structural dynamics of muscle protein phosphorylation. J Muscle Res Cell Motil. 2012;33(6):419-429. DOI: 10.1007/s10974-012-9317-6.Colson B.A., Gruber S.J., Thomas D.D. Structural dynamics of muscle protein phosphorylation. J Muscle Res Cell Motil. 2012;33(6):419-429. DOI: 10.1007/s10974-012-9317-6.Gao Q.Q., McNally E.M. The Dystrophin Complex: Structure, Function, and Implications for Therapy.Compr Physiol. 2015;5(3):1223-1239. DOI: 10.1002/cphy.c140048.Gao Q.Q., McNally E.M. The Dystrophin Complex: Structure, Function, and Implications for Therapy.Compr Physiol. 2015;5(3):1223-1239. DOI: 10.1002/cphy.c140048.Duan D., Goemans N., Takeda S., Mercuri E., Aartsma-Rus A. Duchenne muscular dystrophy. Nat Rev Dis Primers. 2021;7(1):13. DOI: 10.1038/s41572-021-00248-3.Duan D., Goemans N., Takeda S., Mercuri E., Aartsma-Rus A. Duchenne muscular dystrophy. Nat Rev Dis Primers. 2021;7(1):13. DOI: 10.1038/s41572-021-00248-3.Dumont N.A., Wang Y.X., von Maltzahn J., Pasut A., Bentzinger C.F., Brun C.E., Rudnicki M.A. Dystrophin expression in muscle stem cells regulates their polarity and asymmetric division. Nat Med. 2015;21(12):1455-1463. DOI: 10.1038/nm.3990.Dumont N.A., Wang Y.X., von Maltzahn J., Pasut A., Bentzinger C.F., Brun C.E., Rudnicki M.A. Dystrophin expression in muscle stem cells regulates their polarity and asymmetric division. Nat Med. 2015;21(12):1455-1463. DOI: 10.1038/nm.3990.Chang N.C., Chevalier F.P., Rudnicki M.A. Satellite Cells in Muscular Dystrophy - Lost in Polarity. Trends Mol Med. 2016;22:479-496. DOI: 10.1016/j.molmed.2016.04.002.Chang N.C., Chevalier F.P., Rudnicki M.A. Satellite Cells in Muscular Dystrophy - Lost in Polarity. Trends Mol Med. 2016;22:479-496. DOI: 10.1016/j.molmed.2016.04.002.Dumont N.A., Wang Y.X., von Maltzahn J., Pasut A., Bentzinger C.F., Brun C.E., Rudnicki M.A. Dystrophin expression in muscle stem cells regulates their polarity and asymmetric division. Nat Med. 2015;21: 1455-1463. DOI: 10.1038/nm.3990.Dumont N.A., Wang Y.X., von Maltzahn J., Pasut A., Bentzinger C.F., Brun C.E., Rudnicki M.A. Dystrophin expression in muscle stem cells regulates their polarity and asymmetric division. Nat Med. 2015;21: 1455-1463. DOI: 10.1038/nm.3990.Muntoni F., Torelli S., Ferlini A. Dystrophin and mutations: one gene, several proteins, multiple phenotypes. Lancet Neurol. 2003;2(12):731-740. DOI: 10.1016/s1474-4422(03)00585-4.Muntoni F., Torelli S., Ferlini A. Dystrophin and mutations: one gene, several proteins, multiple phenotypes. Lancet Neurol. 2003;2(12):731-740. DOI: 10.1016/s1474-4422(03)00585-4.Rae M.G., O'Malley D. Cognitive dysfunction in Duchenne muscular dystrophy: a possible role for neuromodulatory immune molecules. J Neurophysiol. 2016;116(3):1304-1315. DOI: 10.1152/jn.00248.2016.Rae M.G., O'Malley D. Cognitive dysfunction in Duchenne muscular dystrophy: a possible role for neuromodulatory immune molecules. J Neurophysiol. 2016;116(3):1304-1315. DOI: 10.1152/jn.00248.2016.Ferrero A., Rossi M. Cognitive profile and neuropsychiatric disorders in Becker muscular dystrophy: A systematic review of literature. Neurosci Biobehav Rev. 2022;137:104648. DOI: 10.1016/j.neubiorev.2022.104648.Ferrero A., Rossi M. Cognitive profile and neuropsychiatric disorders in Becker muscular dystrophy: A systematic review of literature. Neurosci Biobehav Rev. 2022;137:104648. DOI: 10.1016/j.neubiorev.2022.104648.Lidov H.G. Dystrophin in the nervous system. Brain Pathol. 1996;6(1):63-77. DOI: 10.1111/j.1750-3639.1996.tb00783.x.Lidov H.G. Dystrophin in the nervous system. Brain Pathol. 1996;6(1):63-77. DOI: 10.1111/j.1750-3639.1996.tb00783.x.Muntoni F., Torelli S., Ferlini A. Dystrophin and mutations: one gene, several proteins, multiple phenotypes. Lancet Neurol. 2003;2:731-740. DOI: 10.1016/s1474-4422(03)00585-4.Muntoni F., Torelli S., Ferlini A. Dystrophin and mutations: one gene, several proteins, multiple phenotypes. Lancet Neurol. 2003;2:731-740. DOI: 10.1016/s1474-4422(03)00585-4.Anderson J.L., Head S.I., Morley J.W. Duchenne muscular dystrophy and brain function M. Hedge, A. Ankala (Eds.), Muscular Dystrophy.Intech. 2012: 91-122. DOI: 10.5772/24928.Anderson J.L., Head S.I., Morley J.W. Duchenne muscular dystrophy and brain function M. Hedge, A. Ankala (Eds.), Muscular Dystrophy.Intech. 2012: 91-122. DOI: 10.5772/24928.Gorecki D.C., Barnard E.A. Specific expression of G-dystrophin (Dp71) in the brain. NeuroReport. 1995;6:893-896. DOI: 10.1097/00001756-199504190-00017Gorecki D.C., Barnard E.A. Specific expression of G-dystrophin (Dp71) in the brain. NeuroReport. 1995;6:893-896. DOI: 10.1097/00001756-199504190-00017Egorova T.V., Zotova E.D., Reshetov D.A., Polikarpova A.V., Vassilieva S.G., Vlodavets D.V., Gavrilov A.A., Ulianov S.V., et al. CRISPR/Cas9-generated mouse model of Duchenne muscular dystrophy recapitulating a newly identified large 430 kb deletion in the human DMD gene. Dis Model Mech. 2019;12(4):dmm037655. DOI: 10.1242/dmm.037655.Egorova T.V., Zotova E.D., Reshetov D.A., Polikarpova A.V., Vassilieva S.G., Vlodavets D.V., Gavrilov A.A., Ulianov S.V., et al. CRISPR/Cas9-generated mouse model of Duchenne muscular dystrophy recapitulating a newly identified large 430 kb deletion in the human DMD gene. Dis Model Mech. 2019;12(4):dmm037655. DOI: 10.1242/dmm.037655.Lim K.R.Q., Nguyen Q., Dzierlega K., Huang Y., Yokota T. CRISPR-Generated Animal Models of Duchenne Muscular Dystrophy. Genes (Basel). 2020;11(3):342. DOI: 10.3390/genes11030342.Lim K.R.Q., Nguyen Q., Dzierlega K., Huang Y., Yokota T. CRISPR-Generated Animal Models of Duchenne Muscular Dystrophy. Genes (Basel). 2020;11(3):342. DOI: 10.3390/genes11030342.Gonzalez L.E., File S.E. A five minute experience in the elevated plus-maze alters the state of the benzodiazepine receptor in the dorsal raphe nucleus. J Neurosci. 1997;17(4):1505-1511. DOI: 10.1523/JNEUROSCI.17-04-01505.1997.Gonzalez L.E., File S.E. A five minute experience in the elevated plus-maze alters the state of the benzodiazepine receptor in the dorsal raphe nucleus. J Neurosci. 1997;17(4):1505-1511. DOI: 10.1523/JNEUROSCI.17-04-01505.1997.Leger M., Quiedeville A., Bouet V., Haelewyn B., Boulouard M., Schumann-Bard P., Freret T. Object recognition test in mice. Nat Protoc. 2013;8(12): 2531-2537. DOI: 10.1038/nprot.2013.155.Leger M., Quiedeville A., Bouet V., Haelewyn B., Boulouard M., Schumann-Bard P., Freret T. Object recognition test in mice. Nat Protoc. 2013;8(12): 2531-2537. DOI: 10.1038/nprot.2013.155.Deacon R.M. Measuring the strength of mice. J Vis Exp. 2013;(76):2610. DOI: 10.3791/2610.Deacon R.M. Measuring the strength of mice. J Vis Exp. 2013;(76):2610. DOI: 10.3791/2610.Gao Q.Q., McNally E.M. The Dystrophin Complex: Structure, Function, and Implications for Therapy.Compr Physiol. 2015;5(3):1223-1239. DOI: 10.1002/cphy.c140048.Gao Q.Q., McNally E.M. The Dystrophin Complex: Structure, Function, and Implications for Therapy.Compr Physiol. 2015;5(3):1223-1239. DOI: 10.1002/cphy.c140048.Koenig M., Hoffman E.P., Bertelson C.J., Monaco A.P., Feener C., Kunkel L.M.Complete cloning of the Duchenne muscular dystrophy (DMD) cDNA and preliminary genomic organization of the DMD gene in normal and affected individuals. Cell. 1987;50:509-517. DOI: 10.1016/0092-8674(87)90504-6.Koenig M., Hoffman E.P., Bertelson C.J., Monaco A.P., Feener C., Kunkel L.M.Complete cloning of the Duchenne muscular dystrophy (DMD) cDNA and preliminary genomic organization of the DMD gene in normal and affected individuals. Cell. 1987;50:509-517. DOI: 10.1016/0092-8674(87)90504-6.Ahn A.H., Kunkel L.M. The structural and functional diversity of dystrophin. Nat Genet.,1993;3:283-291. DOI: 10.1038/ng0493-283.Ahn A.H., Kunkel L.M. The structural and functional diversity of dystrophin. Nat Genet.,1993;3:283-291. DOI: 10.1038/ng0493-283.Duchenne G.B.A. Reserches sur la paralysie musculaire pseudeohypertrofique, ou paralysie myo-sclerosique. Arch Gen Med. 1868;11:5-25, 179-209,305-121, 421-143,552-188Duchenne G.B.A. Reserches sur la paralysie musculaire pseudeohypertrofique, ou paralysie myo-sclerosique. Arch Gen Med. 1868;11:5-25, 179-209,305-121, 421-143,552-188Cotton S., Voudouris N.J., Greenwood K.M.Intelligence and Duchenne muscular dystrophy: full-scale, verbal, and performance intelligence quotients. Dev Med Child Neurol. 2001;43:497-501. DOI: 10.1017/s0012162201000913.Cotton S., Voudouris N.J., Greenwood K.M.Intelligence and Duchenne muscular dystrophy: full-scale, verbal, and performance intelligence quotients. Dev Med Child Neurol. 2001;43:497-501. DOI: 10.1017/s0012162201000913.Hendriksen J.G., Vles J.S. Are males with Duchenne muscular dystrophy at risk for reading disabilities? Pediatr Neurol. 2006;34:296-300. DOI: 10.1016/j.pediatrneurol.2005.08.029.Hendriksen J.G., Vles J.S. Are males with Duchenne muscular dystrophy at risk for reading disabilities? Pediatr Neurol. 2006;34:296-300. DOI: 10.1016/j.pediatrneurol.2005.08.029.Hendriksen J.G., Vles J.S. Neuropsychiatric disorders in males with Duchenne muscular dystrophy: frequency rate of attention-deficit hyperactivity disorder (ADHD), autism spectrum disorder, and obsessive-compulsive disorder. J Child Neurol. 2008;23:477-481. DOI: 10.1177/0883073807309775.Hendriksen J.G., Vles J.S. Neuropsychiatric disorders in males with Duchenne muscular dystrophy: frequency rate of attention-deficit hyperactivity disorder (ADHD), autism spectrum disorder, and obsessive-compulsive disorder. J Child Neurol. 2008;23:477-481. DOI: 10.1177/0883073807309775.Snow W.M., Anderson J.E., Jakobson L.S. Neuropsychological and neurobehavioral functioning in Duchenne muscular dystrophy: a review. Neurosci Biobehav Rev. 2013;37:743-752. DOI: 10.1016/j.neubiorev.2013.03.016.Snow W.M., Anderson J.E., Jakobson L.S. Neuropsychological and neurobehavioral functioning in Duchenne muscular dystrophy: a review. Neurosci Biobehav Rev. 2013;37:743-752. DOI: 10.1016/j.neubiorev.2013.03.016.Etemadifar M., Molaei S. Epilepsy in boys with Duchenne muscular dystrophy. J Res Med Sci. 2004;3:116-119.Etemadifar M., Molaei S. Epilepsy in boys with Duchenne muscular dystrophy. J Res Med Sci. 2004;3:116-119.Goodwin F., Muntoni F., Dubowitz V. Epilepsy in Duchenne and Becker muscular dystrophies. Eur J Paediatr Neurol: Off J Eur Paediatr Neurol Soc. 1997;1:115-119. DOI: 10.1016/s1090-3798(97)80042-6Goodwin F., Muntoni F., Dubowitz V. Epilepsy in Duchenne and Becker muscular dystrophies. Eur J Paediatr Neurol: Off J Eur Paediatr Neurol Soc. 1997;1:115-119. DOI: 10.1016/s1090-3798(97)80042-6Pane M., Messina S., Bruno C., D'Amico A., Villanova M., Brancalion B., Sivo S., Bianco F., et al. Duchenne muscular dystrophy and epilepsy. Neuromuscul Disord. 2013;23(4):313-315. DOI: 10.1016/j.nmd.2013.01.011.Pane M., Messina S., Bruno C., D'Amico A., Villanova M., Brancalion B., Sivo S., Bianco F., et al. Duchenne muscular dystrophy and epilepsy. Neuromuscul Disord. 2013;23(4):313-315. DOI: 10.1016/j.nmd.2013.01.011.Lee A.J., Buckingham E.T., Kauer A.J., Mathews K.D. Descriptive Phenotype of Obsessive Compulsive Symptoms in Males With Duchenne Muscular Dystrophy. J Child Neurol. 2018;33(9):572-579. DOI: 10.1177/0883073818774439.Lee A.J., Buckingham E.T., Kauer A.J., Mathews K.D. Descriptive Phenotype of Obsessive Compulsive Symptoms in Males With Duchenne Muscular Dystrophy. J Child Neurol. 2018;33(9):572-579. DOI: 10.1177/0883073818774439.de Brouwer A.P., Nabuurs S.B., Verhaart I.E., Oudakker A.R., Hordijk R., Yntema H.G., Hordijk-Hos J.M., Voesenek K., et al. A 3-base pair deletion, c.9711_9713del, in DMD results in intellectual disability without muscular dystrophy. Eur J Hum Genet. 2014;22(4):480-485. DOI: 10.1038/ejhg.2013.169.de Brouwer A.P., Nabuurs S.B., Verhaart I.E., Oudakker A.R., Hordijk R., Yntema H.G., Hordijk-Hos J.M., Voesenek K., et al. A 3-base pair deletion, c.9711_9713del, in DMD results in intellectual disability without muscular dystrophy. Eur J Hum Genet. 2014;22(4):480-485. DOI: 10.1038/ejhg.2013.169.Chamberlain J.S., Pearlman J.A., Muzny D.M., Gibbs R.A., Ranier J.E., Caskey C.T., Reeves A.A. Expression of the murine Duchenne muscular dystrophy gene in muscle and brain. Science. 1988;239(4846):1416-1418. DOI: 10.1126/science.3347839.Chamberlain J.S., Pearlman J.A., Muzny D.M., Gibbs R.A., Ranier J.E., Caskey C.T., Reeves A.A. Expression of the murine Duchenne muscular dystrophy gene in muscle and brain. Science. 1988;239(4846):1416-1418. DOI: 10.1126/science.3347839.Lidov H.G., Byers T.J., Kunkel L.M. The distribution of dystrophin in the murine central nervous system: an immunocytochemical study. Neuroscience. 1993;54:167-187. DOI: 10.1016/0306-4522(93)90392-s.Lidov H.G., Byers T.J., Kunkel L.M. The distribution of dystrophin in the murine central nervous system: an immunocytochemical study. Neuroscience. 1993;54:167-187. DOI: 10.1016/0306-4522(93)90392-s.Blake D.J., Kröger S. The neurobiology of Duchenne muscular dystrophy: learning lessons from muscle? Trends Neurosci. 2000;23:92-99. DOI: 10.1016/s0166-2236(99)01510-6.Blake D.J., Kröger S. The neurobiology of Duchenne muscular dystrophy: learning lessons from muscle? Trends Neurosci. 2000;23:92-99. DOI: 10.1016/s0166-2236(99)01510-6.Graciotti L., Minelli A., Minciacchi D., Procopio A., Fulgenzi G. GABAergic miniature spontaneous activity is increased in the CA1 hippocampal region of dystrophic mdx mice Neuromuscul Disord. 2008;18:220-226. DOI: 10.1016/j.nmd.2007.11.009.Graciotti L., Minelli A., Minciacchi D., Procopio A., Fulgenzi G. GABAergic miniature spontaneous activity is increased in the CA1 hippocampal region of dystrophic mdx mice Neuromuscul Disord. 2008;18:220-226. DOI: 10.1016/j.nmd.2007.11.009.Lidov H.G., Selig S., Kunkel L.M. Dp140: a novel 140 kDa CNS transcript from the dystrophin locus. Hum Mol Genet. 1995;4:329-335. DOI: 10.1093/hmg/4.3.329.Lidov H.G., Selig S., Kunkel L.M. Dp140: a novel 140 kDa CNS transcript from the dystrophin locus. Hum Mol Genet. 1995;4:329-335. DOI: 10.1093/hmg/4.3.329.Anderson J.L., Head S.I., Rae C., Morley J.W. Brain function in Duchenne muscular dystrophy. Brain. 2002;125:4-13. DOI: 10.1093/brain/awf012.Anderson J.L., Head S.I., Rae C., Morley J.W. Brain function in Duchenne muscular dystrophy. Brain. 2002;125:4-13. DOI: 10.1093/brain/awf012.Cyrulnik S.E., Hinton V.J. Duchenne muscular dystrophy: a cerebellar disorder? Neurosci Biobehav Rev. 2008:32:486-496. DOI: 10.1016/j.neubiorev.2007.09.001.Cyrulnik S.E., Hinton V.J. Duchenne muscular dystrophy: a cerebellar disorder? Neurosci Biobehav Rev. 2008:32:486-496. DOI: 10.1016/j.neubiorev.2007.09.001.Lidov H.G. Dystrophin in the nervous system. Brain Pathol. 1996;6:63-77. DOI: 10.1111/j.1750-3639.1996.tb00783.x.Lidov H.G. Dystrophin in the nervous system. Brain Pathol. 1996;6:63-77. DOI: 10.1111/j.1750-3639.1996.tb00783.x.Brünig I., Suter A., Knuesel I., Lüscher B., Fritschy J.M. GABAergic terminals are required for postsynaptic clustering of dystrophin but not of GABA(A) receptors and gephyrin. J Neurosci: Off J Soc Neurosci. 2002;22:4805-4813. DOI: 10.1523/JNEUROSCI.22-12-04805.2002.Brünig I., Suter A., Knuesel I., Lüscher B., Fritschy J.M. GABAergic terminals are required for postsynaptic clustering of dystrophin but not of GABA(A) receptors and gephyrin. J Neurosci: Off J Soc Neurosci. 2002;22:4805-4813. DOI: 10.1523/JNEUROSCI.22-12-04805.2002.Kueh S.L., Head S.I., Morley J.W. GABA(A) receptor expression and inhibitory post-synaptic currents in cerebellar Purkinje cells in dystrophin-deficient mdx mice. Clin Exp Pharmacol Physiol. 2008;35:207-210. DOI: 10.1111/j.1440-1681.2007.04816.x.Kueh S.L., Head S.I., Morley J.W. GABA(A) receptor expression and inhibitory post-synaptic currents in cerebellar Purkinje cells in dystrophin-deficient mdx mice. Clin Exp Pharmacol Physiol. 2008;35:207-210. DOI: 10.1111/j.1440-1681.2007.04816.x.Vaillend C., Billard J.M. Facilitated CA1 hippocampal synaptic plasticity in dystrophin-deficient mice: role for GABAA receptors? Hippocampus. 2002;12: 713-717. DOI: 10.1002/hipo.10068.Vaillend C., Billard J.M. Facilitated CA1 hippocampal synaptic plasticity in dystrophin-deficient mice: role for GABAA receptors? Hippocampus. 2002;12: 713-717. DOI: 10.1002/hipo.10068.Craig A.M., Kang Y. Neurexin-neuroligin signaling in synapse development. Curr Opin Neurobiol. 2007;17:43-52. DOI: 10.1016/j.conb.2007.01.011.Craig A.M., Kang Y. Neurexin-neuroligin signaling in synapse development. Curr Opin Neurobiol. 2007;17:43-52. DOI: 10.1016/j.conb.2007.01.011.Albrecht D.E., Froehner S.C. Syntrophins and dystrobrevins: defining the dystrophin scaffold at synapses. Neurosignals. 2002;11:123-129. DOI: 10.1159/000065053.Albrecht D.E., Froehner S.C. Syntrophins and dystrobrevins: defining the dystrophin scaffold at synapses. Neurosignals. 2002;11:123-129. DOI: 10.1159/000065053.

The authors declare that there are no conflicts of interest present.