Survival Motor Neuron (SMN) protein is required for normal mouse liver development
| Autor: | Eva Szunyogova, Thomas H. Gillingwater, Haiyan Zhou, Rachael A. Powis, Simon H. Parson, Francesco Muntoni, Gillian K. Maxwell |
|---|---|
| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Pathology medicine.medical_specialty Multidisciplinary business.industry SMN1 Spinal muscular atrophy Motor neuron SMA medicine.disease Neuromuscular junction 03 medical and health sciences 030104 developmental biology 0302 clinical medicine medicine.anatomical_structure medicine Erythropoiesis Myelopoiesis Liver function business 030217 neurology & neurosurgery |
| Zdroj: | Szunyogova, E, Zhou, H, Maxwell, G K, Powis, R, Muntoni, F, Gillingwater, T & Parson, S H 2016, ' Survival Motor Neuron (SMN) protein is required for normal mouse liver development ', Scientific Reports . https://doi.org/10.1038/srep34635 |
| ISSN: | 2045-2322 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|