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Whole transcriptome analysis of a mouse model for type 2 Gaucher disease identifies potential genetic modifiers

Wednesday, September 14, 2016 — Poster Session I

3:00 p.m. – 4:30 p.m.
FAES Terrace


  • R Grey
  • NS Trivedi
  • A Gonzalez
  • B Berhe
  • AG Elkahloun
  • E Sidransky
  • N Tayebi


As our appreciation of the clinical diversity observed in single-gene Mendelian disorders continues to expand, it is clear that genetic modifiers must play a role. In Gaucher disease, one such example, patients sharing the same mutations in the glucocerebrosidase gene, GBA1, demonstrate vast phenotypic heterogeneity including both neuronopathic and non-neuronopathic forms. Efforts have been directed towards identifying modifier genes or factors that may account for this heterogeneity. We developed a mouse model for type 2 (acute neuronopathic) Gaucher disease by crossing two previously described mouse lines: a knock-in point mutation Leu444Pro (c.1448T>G) mouse and an effectively null gba allele mouse created through the targeted disruption of murine gba (gba-/-). The resulting genotype, Leu444Pro/null, is common among patients with type 2 disease. These mice are not viable, dying perinatally. Additionally, they present with a scaly skin phenotype similar to the skin abnormalities found in some type 2 patients. To assess variations in gene expression in these mice, we performed a whole transcriptome microarray with an Affymetrix GeneChip 2.0 ST array, evaluating RNA from the brains of five of these mouse pups and their appropriate littermate controls. Preliminary analysis suggests that several genes involved in inflammatory pathways may be upregulated in the type 2 mice; specific genes are being validated by real-time PCR. This data may provide new insights into the pathways involved in neuronopathic Gaucher disease and explain some of the phenotypic heterogeneity encountered in this disorder.

Category: Genetics and Genomics