Responsable : Geneviève Gourdon
Il y a plusieurs années, nous avons créé un modèle de souris transgéniques (DMSXL) porteuses de grandes séquences génomiques humaines (45kb) contenant le gène DMPK et la plus grande expansion de triplets répétés CTG introduite chez la souris jusqu’à présent (> 1500CTG). Ces souris présentent une importante instabilité intergénérationelle et somatique des triplets CTG et reproduisent certaines caractéristiques moléculaires et physiologiques de DM1.
Nos recherches suivent 3 axes :
. Mécanismes impliqués dans l’instabilité des trinucléotides répétés dans les modèles cellulaires, murins et dans les familles DM1
. Conséquences moléculaires et physiopathologiques des expansions CTG à l’origine de l’atteinte du système nerveux central et impliquées dans la forme congénitale de la maladie.
. Tests précliniques chez la souris DM1 : phénotypes moléculaires et physiologiques du muscle et du cerveau
Composition du groupe
Geneviève GOURDON, PhD, DR-Inserm, Group leader
Mario GOMES-PEREIRA, PhD, CR-Inserm
Stéphanie TOME, PhD, CR-Inserm
Aline HUGUET-LACHON IE, Université
Hélène BENYAMINE, IE
Anchel GONZALEZ, Post-Doc
Mouli CHAKRABORTY, Post-Doc
Antoine MANGIN, AI
Aurélien CORDIER, AI
Sandra BRAZ, Doctorante
Élodie DANDELOT, Doctorante
Contact : genevieve.gourdon@inserm.fr
Nos dernières publications
- Dincã DM, Lallemant L, González-Barriga A, Cresto N, Braz SO, Sicot G, Pillet L-E, Polvèche H, Magneron P, Huguet-Lachon A, Benyamine H, Azotla-Vilchis CN, Agonizantes-Juárez LE, Tahraoui-Bories J, Martinat C, Hernández-Hernández O, Auboeuf D, Rouach N, Bourgeois CF, Gourdon G, Gomes-Pereira M. Myotonic dystrophy RNA toxicity alters morphology, adhesion and migration of mouse and human astrocytes. Nature Communications, 2022 13: 3841. doi: 10.1038/S41467-022-31594-9.
- Tsai YC, de Pontual L, Heiner C, Stojkovic T, Furling D, Bassez G, Gourdon G, Tomé S. Identification of a CCG-Enriched Expanded Allele in Patients with Myotonic Dystrophy Type 1 Using Amplification-Free Long-Read Sequencing. The Journal Molecular of Diagnostics, 2022. 24: 1143-1154. doi: 10.1016/j.jmoldx.2022.08.003.
- de Pontual L, Tomé S. Overview of the Complex Relationship between Epigenetics Markers, CTG Repeat Instability and Symptoms in Myotonic Dystrophy Type 1. International Journal of Molecular Sciences, 2022. 23: 3477. doi: 10.3390/ijms23073477.
- Potier B, Lallemant L, Parrot S, Huguet-Lachon A, Gourdon G, Dutar P, Gomes-Pereira M. DM1 Transgenic Mice Exhibit Abnormal Neurotransmitter Homeostasis and Synaptic Plasticity in Association with RNA Foci and Mis-Splicing in the Hippocampus. International Journal of Molecular Sciences, 2022. 23: 592. doi: 10.3390/ijms23020592.
- Parrot S, Corscadden A, Lallemant L, Benyamine H, Comte JC, Huguet-Lachon A, Gourdon G, Gomes-Pereira M. Defects in Mouse Cortical Glutamate Uptake Can Be Unveiled In Vivo by a Two-in-One Quantitative Microdialysis. ACS Chemical Neuroscience, 2022. 13: 134–142. doi: 10.1021/acschemneuro.1c00634.
- van Cruchten RTP, van As D, Glennon JC, van Engelen BGM, ‘t Hoen PAC; OPTIMISTIC consortium; ReCognitION consortium including D. Furling & G. Gourdon. Clinical improvement of DM1 patients reflected by reversal of disease-induced gene expression in blood. BMC Medicine. 2022 20(1):395. doi: 10.1186/s12916-022-02591-y.
- Ait Benichou S, Jauvin D, De Serres-Bérard T, Bennett F, Rigo F, Gourdon G, Boutjdir M, Chahine M, Puymirat J. Enhanced Delivery of Ligand-Conjugated Antisense Oligonucleotides (C16-HA-ASO) Targeting Dystrophia Myotonica Protein Kinase Transcripts for the Treatment of Myotonic Dystrophy Type 1. Human Gene Therapy, 2022. 33: 810-820. doi: 10.1089/hum.2022.069.
- Cardinali B, Provenzano C, Izzo M, Voellenkle C, Battistini J, Strimpakos G, Golini E, Mandillo S, Scavizzi F, Raspa M, Perfetti A, Baci D, Lazarevic D, Garcia-Manteiga JM, Gourdon G, Martelli F, Falcone G. Time-controlled and muscle-specific CRISPR/Cas9-mediated deletion of CTG-repeat expansion in the DMPK gene. Mol Ther Nucleic Acids. 2021 Nov 29;27:184-199. doi: 10.1016/j.omtn.2021.11.024.
- L. de Pontual, G. Gourdon and S. Tomé. Identification of new factors inducing CTG.CAG repeat contractions in Myotonic Dystrophy type 1, Med. Sci. (Paris). 2021 37(Hors série), 6-10.
- Koutalianos D, Koutsoulidou A, Mytidou C, Kakouri AC, Oulas A, Tomazou M, Kyriakides TC, Prokopi M, Kapnisis K, Nikolenko N, Turner C, Lusakowska A, Janiszewska K, Papadimas GK, Papadopoulos C, Kararizou E, Spyrou GM, Gourdon G, Zamba Papanicolaou E, Gorman G, Anayiotos A, Lochmüller H, Phylactou LA. miR-223-3p and miR-24-3p as novel serum-based biomarkers for myotonic dystrophy type 1. Mol Ther Methods Clin Dev. 2021 Sep 14;23:169-183. doi: 10.1016/j.omtm.2021.09.007.
- González-Barriga A, Lallemant L, Dincã DM, Braz SO, Polvèche H, Magneron P, Pionneau C, Huguet-Lachon A, Claude J-B, Chhuon C, Guerrera IC, Bourgeois CF, Auboeuf D, Gourdon G, Gomes-Pereira M. Integrative Cell Type-Specific Multi-Omics Approaches Reveal Impaired Programs of Glial Cell Differentiation in Mouse Culture Models of DM1. Frontiers in – Cell Neuroscience – (2021). 15: 126. doi: 10.3389/fncel.2021.662035
- Gomes-Pereira M, Monckton DG. Chronic Exposure to Cadmium and Antioxidants Does Not Affect the Dynamics of Expanded CAG•CTG Trinucleotide Repeats in a Mouse Cell Culture System of Unstable DNA. Frontiers in – Cell Neuroscience – (2021). 14: 606331. doi: 10.3389/fncel.2020.606331.
- Mangin, L. de Pontual, Y-C Tsai, L. Monteil, M. Nizon, P. Boisseau, S.Mercier, J. Ziegle, J. Harting, Cheryl Heiner, G. Gourdon and S. Tomé. Robust detection of somatic mosaicism and repeat interruptions in DM1 families by long- read targeted sequencing. International Journal of Molecular Sciences (2021) 22, 2616.
- Grande V, Hathazi D, O Connor E, Marteau T, Schara-Schmidt U, Hentschel A, Gourdon G, Nikolenko N, Lochmüller H, Roos A. Dysregulation of GSK3β-Target Proteins in Skin Fibroblasts of Myotonic Dystrophy Type 1 (DM1) Patients. Journal of Neuromuscular Disorders (2021) Mar 1. doi: 10.3233/JND-200558.
Tomé S, Dandelot E, Dogan C, Bertrand A, Genevieve D, Pereon Y, French DM-scope consortium, Simon M, Bonnefont JP, Bassez G and Gourdon G. Unusual association of a unique CAG interruption in 5’ of DM1 CTG repeats with intergenerational contraction and low somatic mosaicism. Human mutation, 2018 Jul;39(7):970-982. doi: 10.1002/humu.23531- Jauvin D, Chrétien J, Pandey SK, Martineau L, Jauvin D, Chrétien J, Pandey SK, Martineau L, Revillod L, Bassez G, Huguet-Lachon A, McLeod AR, Gourdon G, Wheeler TM, Thornton CA, Bennett CF and Puymirat J. Targeting DMPK with Antisense Oligonucleotide Improves Muscle Strength in Myotonic Dystrophy Type 1 Mice. Molecular Therapy- Nucleic Acids. 2017 Jun 16;7:465-474. doi: 10.1016/j.omtn.2017.05.007.
- Sicot G, Servais L, Dinca D, Leroy A, Prigogine C, Gall D, Dan B, Medja F, Braz S, Chhuon C, Huguet-Lachon A, Chuon C Nicole A, Gueriba N, Oliveira R, Dan B, Furling D,Swanson MS,Guerrera IC, Cheron G, Gourdon G and Gomes-Pereira M. Downregulation of the glial GLT1 glutamate transporter and Purkinje cell dysfunction in a mouse model of myotonic dystrophy. Cell reports, 2017 Jun 27;19(13):2718-2729. doi: 10.1016/j.celrep.2017.06.006.
- Michel L, Huguet-Lachon A, Gourdon G. Sense and Antisense DMPK RNA Foci Accumulate in DM1 Tissues during Development. PLoS One. 2015 Sep 4;10(9):e0137620. doi: 10.1371/journal.pone.0137620.
- Algalarrondo V, Wahbi K, Sebag F, Gourdon G, Beldjord C, Azibi K, Balse E, Coulombe A, Fischmeister R, Eymard B, Duboc D, Hatem SN. Abnormal sodium current properties contribute to cardiac electrical and contractile dysfunction in a mouse model of myotonic dystrophy type 1. Neuromuscular Disorders. 2015 Apr;25(4):308-20. doi.
- Brouwer J, Huguet A, Nicole A, Munnich A and Gourdon G. Transcriptionally repressive chromatin remodelling and CpG methylation in the presence of expanded CTG-repeats at the DM1 locus. Journal of Nucleic Acids. 2013:567435.
- Decostre V, Vignaud A, Matot B, Huguet A, Ledoux I, Bertil E, Gjata B, Carlier PG, Gourdon G, Hogrel JY. In vivo muscle function follow-up of the DMSXL mouse model of myotonic dystrophy type 1. Neuromuscular Disorders. 2013 Dec;23(12):1016-25
- Hernandez-Hernandez, O, C. Guiraud-Dogan, G, Sicot, A Huguet, S. Luilier, E. Steidl, S. Saenger, E. Marciniak, H. Obriot, C. Chevarin, A. Nicole, L. Revillod, K. Charizanis, K.-Y. Lee, Y. Suzuki, T. Kimura, T. Matsuura, B. Cisneros, M.S. Swanson, F. Trovero, B. Buisson, J.-C. Bizot, M. Hamon, S. Humez, G. Bassez, F. Metzger, L. Buee, A. Munnich, N. Sergeant, G. Gourdon, and M. Gomes-Pereira, Myotonic dystrophy CTG expansion affects synaptic vesicle proteins, neurotransmission and mouse behaviour. Brain, 2013. 136: 957-970.
- Panaite PA, Kuntzer T, Gourdon G, Lobrinus JA, Barakat-Walter I. Functional and histopathological identification of the respiratory failure in a DMSXL transgenic mouse model of myotonic dystrophy. Dis Models & Mechanisms. 2013 May;6(3):622-31. doi: 10.1242/dmm.010512. Epub 2012 Nov 23.`Huguet, A, Medja F, Nicole A, Vignaud A, Guiraud-Dogan C, Ferry A, Decostre V, Hogrel JY, Metzger F, Hoeflich A, Baraibar , Gomes-Pereira M, Puymirat J, Bassez G, Furling D, Munnich A, and Gourdon G. Molecular, Physiological, and Motor Performance Defects in DMSXL Mice Carrying > 1,000 CTG Repeats from the Human DM1 Locus. Plos Genetics, 2012. 8(11).
Autres publications
