King's College London

Research portal

Dymeclin deficiency causes postnatal microcephaly, hypomyelination and reticulum-to-Golgi trafficking defects in mice and humans

Research output: Contribution to journalArticle

Standard

Dymeclin deficiency causes postnatal microcephaly, hypomyelination and reticulum-to-Golgi trafficking defects in mice and humans. / Dupuis, Nina; Fafouri, Assia; Bayot, Aurélien; Kumar, Manoj; Lecharpentier, Tifenn; Ball, Gareth; Edwards, David; Bernard, Véronique; Dournaud, Pascal; Drunat, Séverine; Vermelle-Andrzejewski, Marie; Vilain, Catheline; Abramowicz, Marc; Désir, Julie; Bonaventure, Jacky; Gareil, Nelly; Boncompain, Gaelle; Csaba, Zsolt; Perez, Franck; Passemard, Sandrine; Gressens, Pierre; El Ghouzzi, Vincent.

In: Human Molecular Genetics, 2015.

Research output: Contribution to journalArticle

Harvard

Dupuis, N, Fafouri, A, Bayot, A, Kumar, M, Lecharpentier, T, Ball, G, Edwards, D, Bernard, V, Dournaud, P, Drunat, S, Vermelle-Andrzejewski, M, Vilain, C, Abramowicz, M, Désir, J, Bonaventure, J, Gareil, N, Boncompain, G, Csaba, Z, Perez, F, Passemard, S, Gressens, P & El Ghouzzi, V 2015, 'Dymeclin deficiency causes postnatal microcephaly, hypomyelination and reticulum-to-Golgi trafficking defects in mice and humans', Human Molecular Genetics. https://doi.org/10.1093/hmg/ddv038

APA

Dupuis, N., Fafouri, A., Bayot, A., Kumar, M., Lecharpentier, T., Ball, G., Edwards, D., Bernard, V., Dournaud, P., Drunat, S., Vermelle-Andrzejewski, M., Vilain, C., Abramowicz, M., Désir, J., Bonaventure, J., Gareil, N., Boncompain, G., Csaba, Z., Perez, F., ... El Ghouzzi, V. (2015). Dymeclin deficiency causes postnatal microcephaly, hypomyelination and reticulum-to-Golgi trafficking defects in mice and humans. Human Molecular Genetics. https://doi.org/10.1093/hmg/ddv038

Vancouver

Dupuis N, Fafouri A, Bayot A, Kumar M, Lecharpentier T, Ball G et al. Dymeclin deficiency causes postnatal microcephaly, hypomyelination and reticulum-to-Golgi trafficking defects in mice and humans. Human Molecular Genetics. 2015. https://doi.org/10.1093/hmg/ddv038

Author

Dupuis, Nina ; Fafouri, Assia ; Bayot, Aurélien ; Kumar, Manoj ; Lecharpentier, Tifenn ; Ball, Gareth ; Edwards, David ; Bernard, Véronique ; Dournaud, Pascal ; Drunat, Séverine ; Vermelle-Andrzejewski, Marie ; Vilain, Catheline ; Abramowicz, Marc ; Désir, Julie ; Bonaventure, Jacky ; Gareil, Nelly ; Boncompain, Gaelle ; Csaba, Zsolt ; Perez, Franck ; Passemard, Sandrine ; Gressens, Pierre ; El Ghouzzi, Vincent. / Dymeclin deficiency causes postnatal microcephaly, hypomyelination and reticulum-to-Golgi trafficking defects in mice and humans. In: Human Molecular Genetics. 2015.

Bibtex Download

@article{ad0a232f3c974f11abed78b628cdbea4,
title = "Dymeclin deficiency causes postnatal microcephaly, hypomyelination and reticulum-to-Golgi trafficking defects in mice and humans",
abstract = "Dymeclin is a Golgi-associated protein whose deficiency causes Dyggve-Melchior-Clausen syndrome (DMC, MIM #223800), a rare recessively-inherited spondyloepimetaphyseal dysplasia consistently associated with postnatal microcephaly and intellectual disability. While the skeletal phenotype of DMC patients has been extensively described, very little is known about their cerebral anomalies, which result in brain growth defects and cognitive dysfunction. We used Dymeclin-deficient mice to determine the cause of microcephaly and to identify defective mechanisms at the cellular level. Brain weight and volume were reduced in all mutant mice from postnatal day 5 onward. Mutant mice displayed a narrowing of the frontal cortex, although cortical layers were normally organized. Interestingly, the corpus callosum was markedly thinner, a characteristic we also identified in DMC patients. Consistent with this, the myelin sheath was thinner, less compact and not properly rolled, while the number of mature oligodendrocytes and their ability to produce myelin basic protein were significantly decreased. Finally, cortical neurons from mutant mice and primary fibroblasts from DMC patients displayed substantially delayed endoplasmic reticulum to Golgi trafficking, that could be fully rescued upon Dymeclin re-expression. These findings indicate that Dymeclin is crucial for proper myelination and anterograde neuronal trafficking, two processes that are highly active during postnatal brain maturation.",
author = "Nina Dupuis and Assia Fafouri and Aur{\'e}lien Bayot and Manoj Kumar and Tifenn Lecharpentier and Gareth Ball and David Edwards and V{\'e}ronique Bernard and Pascal Dournaud and S{\'e}verine Drunat and Marie Vermelle-Andrzejewski and Catheline Vilain and Marc Abramowicz and Julie D{\'e}sir and Jacky Bonaventure and Nelly Gareil and Gaelle Boncompain and Zsolt Csaba and Franck Perez and Sandrine Passemard and Pierre Gressens and {El Ghouzzi}, Vincent",
year = "2015",
doi = "10.1093/hmg/ddv038",
language = "English",
journal = "Human Molecular Genetics",
issn = "0964-6906",
publisher = "Oxford University Press",

}

RIS (suitable for import to EndNote) Download

TY - JOUR

T1 - Dymeclin deficiency causes postnatal microcephaly, hypomyelination and reticulum-to-Golgi trafficking defects in mice and humans

AU - Dupuis, Nina

AU - Fafouri, Assia

AU - Bayot, Aurélien

AU - Kumar, Manoj

AU - Lecharpentier, Tifenn

AU - Ball, Gareth

AU - Edwards, David

AU - Bernard, Véronique

AU - Dournaud, Pascal

AU - Drunat, Séverine

AU - Vermelle-Andrzejewski, Marie

AU - Vilain, Catheline

AU - Abramowicz, Marc

AU - Désir, Julie

AU - Bonaventure, Jacky

AU - Gareil, Nelly

AU - Boncompain, Gaelle

AU - Csaba, Zsolt

AU - Perez, Franck

AU - Passemard, Sandrine

AU - Gressens, Pierre

AU - El Ghouzzi, Vincent

PY - 2015

Y1 - 2015

N2 - Dymeclin is a Golgi-associated protein whose deficiency causes Dyggve-Melchior-Clausen syndrome (DMC, MIM #223800), a rare recessively-inherited spondyloepimetaphyseal dysplasia consistently associated with postnatal microcephaly and intellectual disability. While the skeletal phenotype of DMC patients has been extensively described, very little is known about their cerebral anomalies, which result in brain growth defects and cognitive dysfunction. We used Dymeclin-deficient mice to determine the cause of microcephaly and to identify defective mechanisms at the cellular level. Brain weight and volume were reduced in all mutant mice from postnatal day 5 onward. Mutant mice displayed a narrowing of the frontal cortex, although cortical layers were normally organized. Interestingly, the corpus callosum was markedly thinner, a characteristic we also identified in DMC patients. Consistent with this, the myelin sheath was thinner, less compact and not properly rolled, while the number of mature oligodendrocytes and their ability to produce myelin basic protein were significantly decreased. Finally, cortical neurons from mutant mice and primary fibroblasts from DMC patients displayed substantially delayed endoplasmic reticulum to Golgi trafficking, that could be fully rescued upon Dymeclin re-expression. These findings indicate that Dymeclin is crucial for proper myelination and anterograde neuronal trafficking, two processes that are highly active during postnatal brain maturation.

AB - Dymeclin is a Golgi-associated protein whose deficiency causes Dyggve-Melchior-Clausen syndrome (DMC, MIM #223800), a rare recessively-inherited spondyloepimetaphyseal dysplasia consistently associated with postnatal microcephaly and intellectual disability. While the skeletal phenotype of DMC patients has been extensively described, very little is known about their cerebral anomalies, which result in brain growth defects and cognitive dysfunction. We used Dymeclin-deficient mice to determine the cause of microcephaly and to identify defective mechanisms at the cellular level. Brain weight and volume were reduced in all mutant mice from postnatal day 5 onward. Mutant mice displayed a narrowing of the frontal cortex, although cortical layers were normally organized. Interestingly, the corpus callosum was markedly thinner, a characteristic we also identified in DMC patients. Consistent with this, the myelin sheath was thinner, less compact and not properly rolled, while the number of mature oligodendrocytes and their ability to produce myelin basic protein were significantly decreased. Finally, cortical neurons from mutant mice and primary fibroblasts from DMC patients displayed substantially delayed endoplasmic reticulum to Golgi trafficking, that could be fully rescued upon Dymeclin re-expression. These findings indicate that Dymeclin is crucial for proper myelination and anterograde neuronal trafficking, two processes that are highly active during postnatal brain maturation.

U2 - 10.1093/hmg/ddv038

DO - 10.1093/hmg/ddv038

M3 - Article

C2 - 25652408

JO - Human Molecular Genetics

JF - Human Molecular Genetics

SN - 0964-6906

ER -

View graph of relations

© 2018 King's College London | Strand | London WC2R 2LS | England | United Kingdom | Tel +44 (0)20 7836 5454