Gaucher disease in sheep

J Inherit Metab Dis. 2011 Feb;34(1):209-15. doi: 10.1007/s10545-010-9230-3. Epub 2010 Oct 27.


Gaucher disease, an autosomal recessive lysosomal storage disorder caused by mutations in the β-glucocerebrosidase gene, was recently discovered in sheep on a "Southdown" sheep stud in Victoria, Australia. Clinical signs include neuropathy, thickened leathery skin, and ichthyosis, with lambs unable to stand from birth. Affected lambs were found to be deficient in glucocerebrosidase activity, and mutational analysis found them to be homozygous for the missense mutations c.1142G>A (p.C381Y) and c.1400C>T (p.P467L). In addition, four silent mutations were detected (c.777C>A [p.Y259Y], c1203A>G [p.Q401Q], c.1335T>C [p.I445I], c.1464C>G [p.L488L]). The human equivalent [C342Y] to the C381Y mutation leads to an acute neuronopathic phenotype in patients. Identification of an acute neuronopathic form of Gaucher disease in sheep provides a large animal model that will enable studies of pathology and evaluation of therapies to treat this common lysosomal storage disorder.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Cells, Cultured
  • DNA Mutational Analysis
  • Gaucher Disease / diagnosis*
  • Gaucher Disease / pathology
  • Gaucher Disease / veterinary*
  • Glucosylceramidase / analysis
  • Glucosylceramidase / genetics
  • Glucosylceramidase / metabolism
  • Homozygote
  • Humans
  • Molecular Sequence Data
  • Mutation, Missense
  • Sequence Homology, Amino Acid
  • Sheep
  • Sheep Diseases / diagnosis*
  • Sheep Diseases / etiology
  • Sheep Diseases / pathology


  • Glucosylceramidase

Associated data

  • GENBANK/J03059
  • GENBANK/M16328
  • OMIM/230800
  • OMIM/230900
  • OMIM/231000
  • OMIM/606463
  • SWISSPROT/P04062