Imperial College London
Alternate

ProfessorVictorTybulewicz

Faculty of Medicine, Department of Immunology and Inflammation

Visiting Professor
 
 
 
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Contact

 

+44 (0)20 3796 1612v.tybulewicz Website CV

 
 
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Location

 

L2-2720Francis Crick InstituteThe Francis Crick Institute

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Summary

 

Publications

Citation

BibTex format

@article{Watson-Scales:2018:10.1371/journal.pgen.1007383,
author = {Watson-Scales, S and Kalmar, B and Lana-Elola, E and Gibbins, D and La, Russa F and Wiseman, F and Williamson, M and Saccon, R and Slender, A and Olerinyova, A and Mahmood, R and Nye, E and Cater, H and Wells, S and Yu, YE and Bennett, DLH and Greensmith, L and Fisher, EMC and Tybulewicz, VLJ},
doi = {10.1371/journal.pgen.1007383},
journal = {PLoS Genetics},
title = {Analysis of motor dysfunction in Down Syndrome reveals motor neuron degeneration},
url = {http://dx.doi.org/10.1371/journal.pgen.1007383},
volume = {14},
year = {2018}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - Down Syndrome (DS) is caused by trisomy of chromosome 21 (Hsa21) and results in a spectrum of phenotypes including learning and memory deficits, and motor dysfunction. It has been hypothesized that an additional copy of a few Hsa21 dosage-sensitive genes causes these phenotypes, but this has been challenged by observations that aneuploidy can cause phenotypes by the mass action of large numbers of genes, with undetectable contributions from individual sequences. The motor abnormalities in DS are relatively understudied-the identity of causative dosage-sensitive genes and the mechanism underpinning the phenotypes are unknown. Using a panel of mouse strains with duplications of regions of mouse chromosomes orthologous to Hsa21 we show that increased dosage of small numbers of genes causes locomotor dysfunction and, moreover, that the Dyrk1a gene is required in three copies to cause the phenotype. Furthermore, we show for the first time a new DS phenotype: loss of motor neurons both in mouse models and, importantly, in humans with DS, that may contribute to locomotor dysfunction.
AU  - Watson-Scales,S
AU  - Kalmar,B
AU  - Lana-Elola,E
AU  - Gibbins,D
AU  - La,Russa F
AU  - Wiseman,F
AU  - Williamson,M
AU  - Saccon,R
AU  - Slender,A
AU  - Olerinyova,A
AU  - Mahmood,R
AU  - Nye,E
AU  - Cater,H
AU  - Wells,S
AU  - Yu,YE
AU  - Bennett,DLH
AU  - Greensmith,L
AU  - Fisher,EMC
AU  - Tybulewicz,VLJ
DO  - 10.1371/journal.pgen.1007383
PY  - 2018///
SN  - 1553-7390
TI  - Analysis of motor dysfunction in Down Syndrome reveals motor neuron degeneration
T2  - PLoS Genetics
UR  - http://dx.doi.org/10.1371/journal.pgen.1007383
UR  - https://www.ncbi.nlm.nih.gov/pubmed/29746474
UR  - http://hdl.handle.net/10044/1/60251
VL  - 14
ER  -
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