A dog model for centronuclear myopathy carrying the most common DNM2 mutation.
Congenital myopathy
Dynamin
Large animal model
MTM1
Neuromuscular disorder
T-tubules
Journal
Disease models & mechanisms
ISSN: 1754-8411
Titre abrégé: Dis Model Mech
Pays: England
ID NLM: 101483332
Informations de publication
Date de publication:
01 04 2022
01 04 2022
Historique:
received:
28
07
2021
accepted:
21
02
2022
pubmed:
5
3
2022
medline:
16
4
2022
entrez:
4
3
2022
Statut:
ppublish
Résumé
Mutations in DNM2 cause autosomal dominant centronuclear myopathy (ADCNM), a rare disease characterized by skeletal muscle weakness and structural anomalies of the myofibres, including nuclear centralization and mitochondrial mispositioning. Following the clinical report of a Border Collie male with exercise intolerance and histopathological hallmarks of CNM on the muscle biopsy, we identified the c.1393C>T (R465W) mutation in DNM2, corresponding to the most common ADCNM mutation in humans. In order to establish a large animal model for longitudinal and preclinical studies on the muscle disorder, we collected sperm samples from the Border Collie male and generated a dog cohort for subsequent clinical, genetic and histological investigations. Four of the five offspring carried the DNM2 mutation and showed muscle atrophy and a mildly impaired gait. Morphological examinations of transverse muscle sections revealed CNM-typical fibres with centralized nuclei and remodelling of the mitochondrial network. Overall, the DNM2-CNM dog represents a faithful animal model for the human disorder, allows the investigation of ADCNM disease progression, and constitutes a valuable complementary tool to validate innovative therapies established in mice.
Identifiants
pubmed: 35244154
pii: 274622
doi: 10.1242/dmm.049219
pmc: PMC9016898
pii:
doi:
Substances chimiques
DNM2 protein, human
EC 3.6.5.5
Dynamin II
EC 3.6.5.5
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Informations de copyright
© 2022. Published by The Company of Biologists Ltd.
Déclaration de conflit d'intérêts
Competing interests J.L. is co-founder of Dynacure.
Références
J Neuromuscul Dis. 2015 Jun 4;2(2):167-174
pubmed: 27858727
BMC Neurol. 2015 Oct 30;15:223
pubmed: 26517984
EMBO J. 2016 Nov 2;35(21):2270-2284
pubmed: 27670760
EMBO J. 2010 Nov 3;29(21):3593-606
pubmed: 20935625
Proc Natl Acad Sci U S A. 2010 Aug 17;107(33):14697-702
pubmed: 20682747
Skelet Muscle. 2019 May 27;9(1):15
pubmed: 31133066
Front Vet Sci. 2020 Mar 11;7:80
pubmed: 32219101
PLoS Genet. 2013 Jun;9(6):e1003430
pubmed: 23754947
Nat Genet. 2005 Mar;37(3):289-94
pubmed: 15731758
Neuromuscul Disord. 2020 May;30(5):353-359
pubmed: 32417001
Clin Immunol. 2001 Feb;98(2):235-43
pubmed: 11161980
Skelet Muscle. 2015 Jan 27;5(1):1
pubmed: 25664165
Hum Mol Genet. 2010 Dec 15;19(24):4820-36
pubmed: 20858595
Nature. 2011 Sep 18;477(7366):556-60
pubmed: 21927000
Sci Transl Med. 2014 Jan 22;6(220):220ra10
pubmed: 24452262
Proc Natl Acad Sci U S A. 2018 Oct 23;115(43):11066-11071
pubmed: 30291191
Hum Mol Genet. 2019 Dec 15;28(24):4067-4077
pubmed: 31628461
Nat Genet. 1996 Jun;13(2):175-82
pubmed: 8640223
Hum Mol Genet. 2008 Jul 15;17(14):2132-43
pubmed: 18434328
Neuromuscul Disord. 2009 Nov;19(11):788-96
pubmed: 19800232
Nat Genet. 2005 Nov;37(11):1207-9
pubmed: 16227997
Genet Mol Biol. 2015 May;38(2):147-51
pubmed: 26273216
Nat Rev Mol Cell Biol. 2012 Jan 11;13(2):75-88
pubmed: 22233676
Hum Mol Genet. 2005 Jun 1;14(11):1417-27
pubmed: 15829503
Mol Biol Cell. 2009 Aug;20(15):3561-71
pubmed: 19515832
Nat Genet. 2007 Sep;39(9):1134-9
pubmed: 17676042
J Biol Chem. 2010 Jul 23;285(30):22753-7
pubmed: 20529869
Brain. 2014 Dec;137(Pt 12):3160-70
pubmed: 25260562
Mol Ther. 2012 Nov;20(11):2120-33
pubmed: 22968479
Hum Mutat. 2012 Jun;33(6):949-59
pubmed: 22396310
J Small Anim Pract. 2012 Oct;53(10):608-12
pubmed: 23013377
Nature. 2005 Dec 1;438(7068):590-6
pubmed: 16319878
J Gene Med. 2011 Sep;13(9):497-506
pubmed: 22144143
Mol Biol Cell. 1997 Dec;8(12):2553-62
pubmed: 9398675
J Neuromuscul Dis. 2019;6(4):421-451
pubmed: 31450509
Science. 2018 Oct 5;362(6410):86-91
pubmed: 30166439