The Cerebellum

, Volume 16, Issue 2, pp 462–472

Defining Trends in Global Gene Expression in Arabian Horses with Cerebellar Abiotrophy

Original Paper

DOI: 10.1007/s12311-016-0823-8

Cite this article as:
Scott, E.Y., Penedo, M.C.T., Murray, J.D. et al. Cerebellum (2017) 16: 462. doi:10.1007/s12311-016-0823-8


Equine cerebellar abiotrophy (CA) is a hereditary neurodegenerative disease that affects the Purkinje neurons of the cerebellum and causes ataxia in Arabian foals. Signs of CA are typically first recognized either at birth to any time up to 6 months of age. CA is inherited as an autosomal recessive trait and is associated with a single nucleotide polymorphism (SNP) on equine chromosome 2 (13074277G>A), located in the fourth exon of TOE1 and in proximity to MUTYH on the antisense strand. We hypothesize that unraveling the functional consequences of the CA SNP using RNA-seq will elucidate the molecular pathways underlying the CA phenotype. RNA-seq (100 bp PE strand-specific) was performed in cerebellar tissue from four CA-affected and five age-matched unaffected horses. Three pipelines for differential gene expression (DE) analysis were used (Tophat2/Cuffdiff2, Kallisto/EdgeR, and Kallisto/Sleuth) with 151 significant DE genes identified by all three pipelines in CA-affected horses. TOE1 (Log2(foldchange) = 0.92, p = 0.66) and MUTYH (Log2(foldchange) = 1.13, p = 0.66) were not differentially expressed. Among the major pathways that were differentially expressed, genes associated with calcium homeostasis and specifically expressed in Purkinje neurons, CALB1 (Log2(foldchange) = −1.7, p < 0.01) and CA8 (Log2(foldchange) = −0.97, p < 0.01), were significantly down-regulated, confirming loss of Purkinje neurons. There was also a significant up-regulation of markers for microglial phagocytosis, TYROBP (Log2(foldchange) = 1.99, p < 0.01) and TREM2 (Log2(foldchange) = 2.02, p < 0.01). These findings reaffirm a loss of Purkinje neurons in CA-affected horses along with a potential secondary loss of granular neurons and activation of microglial cells.


Cerebellar abiotrophy Horse Calcium Microglial activation RNA-seq 

Supplementary material

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Copyright information

© Springer Science+Business Media New York 2016

Authors and Affiliations

  1. 1.Department of Animal ScienceUniversity of CaliforniaDavisUSA
  2. 2.Veterinary Genetics Laboratory, School of Veterinary MedicineUniversity of CaliforniaDavisUSA
  3. 3.Department of Population Health and Reproduction, School of Veterinary MedicineUniversity of CaliforniaDavisUSA

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