Szunyogova, E;
Zhou, H;
Maxwell, GK;
Powis, RA;
Francesco, M;
Gillingwater, TH;
Parson, SH;
(2016)
Survival Motor Neuron (SMN) protein is required for normal mouse liver development.
SCIENTIFIC REPORTS
, 6
(ARTN 346)
10.1038/srep34635.
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Abstract
Spinal Muscular Atrophy (SMA) is caused by mutation or deletion of the survival motor neuron 1 (SMN1) gene. Decreased levels of, cell-ubiquitous, SMN protein is associated with a range of systemic pathologies reported in severe patients. Despite high levels of SMN protein in normal liver, there is no comprehensive study of liver pathology in SMA. We describe failed liver development in response to reduced SMN levels, in a mouse model of severe SMA. The SMA liver is dark red, small and has: iron deposition; immature sinusoids congested with blood; persistent erythropoietic elements and increased immature red blood cells; increased and persistent megakaryocytes which release high levels of platelets found as clot-like accumulations in the heart. Myelopoiesis in contrast, was unaffected. Further analysis revealed significant molecular changes in SMA liver, consistent with the morphological findings. Antisense treatment from birth with PMO25, increased lifespan and ameliorated all morphological defects in liver by postnatal day 21. Defects in the liver are evident at birth, prior to motor system pathology, and impair essential liver function in SMA. Liver is a key recipient of SMA therapies, and systemically delivered antisense treatment, completely rescued liver pathology. Liver therefore, represents an important therapeutic target in SMA.
| Type: | Article |
|---|---|
| Title: | Survival Motor Neuron (SMN) protein is required for normal mouse liver development |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1038/srep34635 |
| Publisher version: | http://dx.doi.org/10.1038/srep34635 |
| Additional information: | © The Author(s) 2016. This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ |
| Keywords: | Science & Technology, Multidisciplinary Sciences, Science & Technology - Other Topics, SPINAL-MUSCULAR-ATROPHY, MORPHOLINO ANTISENSE OLIGOMER, CONGENITAL HEART-DISEASE, WERDNIG-HOFFMANN-DISEASE, NEUROMUSCULAR-JUNCTION, CARDIAC DEFECTS, MODEL, MICE, RESCUE, IRON |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL GOS Institute of Child Health UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL GOS Institute of Child Health > Developmental Neurosciences Dept UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL GOS Institute of Child Health > Genetics and Genomic Medicine Dept |
| URI: | https://discovery.ucl.ac.uk/id/eprint/1520034 |
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