В6.А-Dysfprmd/GeneJ mice as a genetic model of dysferlinopathy
- 作者: Korokin M.1, Kuzubova E.1, Radchenko A.1, Deev R.2,3, Yakovlev I.4, Deikin A.1, Zhunusov N.1, Krayushkina A.1, Pokrovsky V.1, Puchenkova O.1, Chaprov K.1,5, Ekimova N.1, Bardakov S.6, Chernova O.2, Emelin A.1,2, Limaev I.2
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隶属关系:
- Belgorod State National Research University
- North-Western State Medical University named after I.I. Mechnikov
- PJSC “Human Stem Cells Institute”
- LLC “Genotarget”
- Institute of Physiologically Active Compounds at Federal Research Center of Problems of Chemical Physics and Medicinal Chemistry, Russian Academy of Sciences (IPAC RAS)
- S. M. Kirov Military Medical Academy
- 期: 卷 10, 编号 5 (2022)
- 页面: 483-496
- 栏目: ORIGINAL ARTICLES
- URL: https://journals.rcsi.science/2307-9266/article/view/252954
- DOI: https://doi.org/10.19163/2307-9266-2022-10-5-483-496
- ID: 252954
如何引用文章
详细
The aim of the work was behavioral and pathomorphological phenotyping of the mice knockout for the DYSF gene, which plays an important role in the development and progression of dysferlinopathy.
Materials and methods. A B6.A-Dysfprmd/GeneJ (Bla/J) mice subline was used in the work. During the study, a muscle activity was determined basing on the following tests: “Inverted grid”, “Grip strength”, “Wire Hanging”, “Weight-loaded swimming”, Vertical Pole”. Histological and immunofluorescent examinations of skeletal muscles (m. gastrocnemius, m. tibialis) were performed. The presence and distribution of the dysferlin protein was assessed, and general histological changes in the skeletal muscle characteristics of mice at the age of 12 and 24 weeks, were described. A morphometric analysis with the determination of the following parameters was performed: the proportion of necrotic muscle fibers; the proportion of fibers with centrally located nuclei; the mean muscle fiber diameter.
Results. The “Grip strength” test and the “Weight-loaded swimming” test revealed a decrease in the strength of the forelimbs and endurance in the studied mice of the Bla/J subline compared to the control line. The safety of physical performance was checked using the “Wire Hanging” test and the “Vertical Pole” test, which showed a statistically significant difference between the studied mice and control. The coordination of movements and muscle strength of the limbs examined in the “Inverted Grid” test did not change in these age marks. Decreased grip strength of the forelimbs, decreased physical endurance with age, reflects the progression of the underlying muscular disease. Histological methods in the skeletal muscles revealed signs of a myopathic damage pattern: necrotic muscle fibers, moderate lympho-macrophage infiltration, an increase in the proportion of fibers with centrally located nuclei, and an increase in the average fiber diameter compared to the control. The dysferlin protein was not found out in the muscle tissues.
Conclusion. Taking into account the results of the tests performed, it was shown that the absence of Dysf-/- gene expression in Bla/J subline mice led to muscular dystrophy with the onset of the development of phenotypic disease manifestations at the age of 12 weeks and their peak at 24 weeks. Histopathological phenotypic manifestations of the disease are generally nonspecific and corresponded to the data of intravital pathoanatomical examination in diferlinopathy patients. The mice of the studied subline Bla/J are a representative model of dysferlinopathy and can be used to evaluate new therapeutic agents for the treatment of this disease.
作者简介
Mikhail Korokin
Belgorod State National Research University
编辑信件的主要联系方式.
Email: korokin@bsu.edu.ru
ORCID iD: 0000-0001-5402-0697
Doctor of Sciences (Medicine), Associate Professor of the Department of Pharmacology and Clinical Pharmacology
俄罗斯联邦, 85, Pobedy Str., Belgorod, 308015Elena Kuzubova
Belgorod State National Research University
Email: 1015artek1015@mail.ru
ORCID iD: 0000-0003-2425-5027
Junior Researcher, Laboratory of Genetic Technologies and Gene Editing for Biomedicine and Veterinary Medicine
俄罗斯联邦, 85, Pobedy Str., Belgorod, 308015Alexandra Radchenko
Belgorod State National Research University
Email: sandrinkaradchenko@gmail.com
ORCID iD: 0000-0002-4554-2116
Junior Researcher of Laboratory of Genetic Technologies and Gene Editing for Biomedicine and Veterinary Medicine
俄罗斯联邦, 85, Pobedy Str., Belgorod, 308015Roman Deev
North-Western State Medical University named after I.I. Mechnikov; PJSC “Human Stem Cells Institute”
Email: romdey@gmail.com
ORCID iD: 0000-0001-8389-3841
Candidate of Sciences (Medicine), Associate Professor, Acting Head of the Department of Pathological Anatomy, Director for Science
俄罗斯联邦, 41, Kirochnaya Str., St. Petersburg, 191015; Bld. A, 10, 60-Letiya Oktyabrya Ave., Moscow, 117292Ivan Yakovlev
LLC “Genotarget”
Email: ivan@ivan-ya.ru
ORCID iD: 0000-0001-8127-4078
General Director
俄罗斯联邦, 48/7, Nobel Str., Skolkovo Innovation Center, Moscow, 121205Aleksey Deikin
Belgorod State National Research University
Email: alexei@deikin.ru
ORCID iD: 0000-0001-9960-0863
Candidate of Sciences (Biology), Associate Professor of the Department of Pharmacology and Clinical Pharmacology
俄罗斯联邦, 85, Pobedy Str., Belgorod, 308015Nikita Zhunusov
Belgorod State National Research University
Email: nzhunu@mail.ru
ORCID iD: 0000-0002-1969-3615
Assistant of the Department of Pharmacology and Clinical Pharmacology
俄罗斯联邦, 85, Pobedy Str., Belgorod, 308015Anastasia Krayushkina
Belgorod State National Research University
Email: krayushkina_2016@mail.ru
ORCID iD: 0000-0002-6830-3820
Assistant of the Department of Pharmacology and Clinical Pharmacology
俄罗斯联邦, 85, Pobedy Str., Belgorod, 308015Vladimir Pokrovsky
Belgorod State National Research University
Email: pokrovskiy@bsu.edu.ru
ORCID iD: 0000-0002-1493-3376
Assistant of the Department of Pharmacology and Clinical Pharmacology
俄罗斯联邦, 85, Pobedy Str., Belgorod, 308015Olesya Puchenkova
Belgorod State National Research University
Email: lesya759@yandex.ru
ORCID iD: 0000-0002-7657-0937
Resident of the Medical Institute
俄罗斯联邦, 85, Pobedy Str., Belgorod, 308015Kirill Chaprov
Belgorod State National Research University; Institute of Physiologically Active Compounds at Federal Research Center of Problems of Chemical Physics and Medicinal Chemistry, Russian Academy of Sciences (IPAC RAS)
Email: chapkir@gmail.com
ORCID iD: 0000-0002-0258-1879
Junior Researcher of Laboratory for Modeling and Gene Therapy of Human Diseases, Junior Researcher
俄罗斯联邦, 85, Pobedy Str., Belgorod, 308015; 1, Severny Driveway, Chernogolovka, 142432Natalya Ekimova
Belgorod State National Research University
Email: ekimova@bsu.edu.ru
ORCID iD: 0000-0002-3629-048X
Assistant of the Department of Pharmacology and Clinical Pharmacology
俄罗斯联邦, 85, Pobedy Str., Belgorod, 308015Sergey Bardakov
S. M. Kirov Military Medical Academy
Email: epistaxis@mail.ru
ORCID iD: 0000-0002-3804-6245
Neurologist, Lecturer of the Department of Nervous Diseases
俄罗斯联邦, 6, Academician Lebedev Str., St. Petersburg, 194044Olga Chernova
North-Western State Medical University named after I.I. Mechnikov
Email: olgachernova92@yandex.ru
ORCID iD: 0000-0001-6310-9319
Assistant of the Department of Human Morphology
俄罗斯联邦, 41, Kirochnaya Str., St. Petersburg, 191015Aleksey Emelin
Belgorod State National Research University; North-Western State Medical University named after I.I. Mechnikov
Email: eamar40rn@gmail.com
ORCID iD: 0000-0003-4109-0105
Assistant of the Department of Pathological Anatomy, Postgraduate Student of the Department of Pathological Anatomy
俄罗斯联邦, 85, Pobedy Str., Belgorod, 308015; 41, Kirochnaya Str., St. Petersburg, 191015Igor Limaev
North-Western State Medical University named after I.I. Mechnikov
Email: ig.limaev@gmail.com
ORCID iD: 0000-0002-0994-9787
Senior Assistant of the Department of Pathological Anatomy
俄罗斯联邦, 41, Kirochnaya Str., St. Petersburg, 191015参考
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