Motor Deficits and Cerebellar Atrophy in Elovl5 Knock Out Mice

Abstract

Spino-Cerebellar-Ataxia type 38 (SCA38) is caused by missense mutations in the very long chain fatty acid elongase 5 gene, ELOVL5. The main clinical findings in this disease are ataxia, hyposmia and cerebellar atrophy. Mice in which Elovl5 has been knocked out represent a model of the loss of function hypothesis of SCA38. In agreement with this hypothesis, Elovl5 knock out mice reproduced the main symptoms of patients, motor deficits at the beam balance test and hyposmia. The cerebellar cortex of Elovl5 knock out mice showed a reduction of thickness of the molecular layer, already detectable at 6 months of age, confirmed at 12 and 18 months. The total perimeter length of the Purkinje cell (PC) layer was also reduced in Elovl5 knock out mice. Since Elovl5 transcripts are expressed by PCs, whose dendrites are a major component of the molecular layer, we hypothesized that an alteration of their dendrites might be responsible for the reduced thickness of this layer. Reconstruction of the dendritic tree of biocytin-filled PCs, followed by Sholl analysis, showed that the distribution of distal dendrites was significantly reduced in Elovl5 knock out mice. Dendritic spine density was conserved. These results suggest that Elovl5 knock out mice recapitulate SCA38 symptoms and that their cerebellar atrophy is due, at least in part, to a reduced extension of PC dendritic arborization.

Pianp deficiency links GABAB receptor signaling and hippocampal and cerebellar neuronal cell composition to autism-like behavior

“…PianpKO mice, however, did not show deficits in basic motor functions. In a mouse model of spinocerebellar ataxia these tests also revealed normal results [44]. Mice, as four-legged animals, might be less sensitive to cerebellar alterations in terms of motor functions.…”

Extracellular S100β Disrupts Bergman Glia Morphology and Synaptic Transmission in Cerebellar Purkinje Cells

“…The thickness of the molecular layer correlates with the length of the PC dendritic tree [45]. To examine the approximate length of PCs’ dendrites, we measured the thickness of the molecular layer and found that it was significantly reduced by S100β (Figure 4A,B).…”

Clinical and Functional Characterization of a Missense ELF2 Variant in a CANVAS Family

“…This gene is involved in the long-chain fatty acids elongation cycle, and it is highly expressed in Purkinje cells. Furthermore, the ELOVL5 -/- mice develop ataxia and motor impairment during the balance beam test ( Hoxha et al, 2017 ). Several neurological diseases, particularly hereditary spastic paraplegias ( Dick et al, 2010 ; Tesson et al, 2012 ; Boukhris et al, 2013 ; Martin et al, 2013 ) display alterations of lipid metabolism.…”

“…We also investigated the effect of mutant ELF2 on ATNX2 and ELOVL5 expression levels, since these genes are a direct target of ELF2, according to Curated Transcription Factor Targets Dataset (TRANSFAC), and both have been associated with SCA2 and SCA38 ( Scoles et al, 2012 ; Di Gregorio et al, 2014 ; Hoxha et al, 2017 ).…”