Renal pathology in a mouse model of severe Spinal Muscular Atrophy is associated with downregulation of Glial Cell-Line Derived Neurotrophic Factor (GDNF)

Hazel Allardyce, Daniela Kuhn, Elena Hernandez Gerez, Niko Hensel, Yu‐Ting Huang, Kiterie Faller, Thomas H. Gillingwater, Fabio Quondamatteo, Peter Claus, Simon H. Parson* (Corresponding Author)

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

12 Citations (Scopus)
7 Downloads (Pure)


Spinal muscular atrophy (SMA) occurs as a result of cell-ubiquitous depletion of the essential survival motor neuron (SMN) protein. Characteristic disease pathology is driven by a particular vulnerability of the ventral motor neurons of the spinal cord to decreased SMN. Perhaps not surprisingly, many other organ systems are also impacted by SMN depletion. The normal kidney expresses very high levels of SMN protein, equivalent to those found in the nervous system and liver, and levels are dramatically lowered by ~90-95% in mouse models of SMA. Taken together, these data suggest that renal pathology may be present in SMA. We have addressed this using an established mouse model of severe SMA. Nephron number, as assessed by gold standard stereological techniques, was significantly reduced. In addition, morphological assessment showed decreased renal vasculature, particularly of the glomerular capillary knot, dysregulation of nephrin and collagen IV, and ultrastructural changes in the trilaminar filtration layers of the nephron. To explore the molecular drivers underpinning this process, we correlated these findings with quantitative PCR measurements and protein analyses of glial cell-line-derived neurotrophic factor, a crucial factor in ureteric bud branching and subsequent nephron development. Glial cell-line-derived neurotrophic factor levels were significantly reduced at early stages of disease in SMA mice. Collectively, these findings reveal significant renal pathology in a mouse model of severe SMA, further reinforcing the need to develop and administer systemic therapies for this neuromuscular disease.

Original languageEnglish
Pages (from-to)2365-2378
Number of pages14
JournalHuman Molecular Genetics
Issue number14
Early online date26 Jun 2020
Publication statusPublished - 15 Jul 2020

Bibliographical note

We would like to acknowledge the Microscopy and Histology
Core Facility members; Kevin Mackenzie, Debbie Wilkinson,
Gillian Milne and Lucy Wight at the University of Aberdeen, and Margaret Mullin at the Glasgow Imaging Facility, University of Glasgow, for their support, assistance and use of the facilities.
SMA Europe and an Anatomical Society PhD Studentship to
S.H.P. and H.A.; the Deutsche Muskelstiftung (E-2019-01 to P.C.)


  • Non-neuronal
  • Kidney
  • Sclerosis
  • Nephrin
  • Collagen IV
  • MICE


Dive into the research topics of 'Renal pathology in a mouse model of severe Spinal Muscular Atrophy is associated with downregulation of Glial Cell-Line Derived Neurotrophic Factor (GDNF)'. Together they form a unique fingerprint.

Cite this