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Gaucher disease in sheep

  • Original Article
  • Published:
Journal of Inherited Metabolic Disease

Abstract

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.

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Abbreviations

GD:

Gaucher disease

GBA:

β-glucocerebrosidase

NCBI:

National Center for Biotechnology Information

PCR:

polymerase chain reaction

mRNA:

messenger RNA

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Acknowledgements

We acknowledge funding support from the National Health and Medical Research Council of Australia for this study. We are grateful to Bev Fong at SA Pathology, Women's and Children's Hospital in Adelaide for the lysosomal enzyme assays, Kathy Nelson at SA Pathology, Women's and Children's Hospital in Adelaide for her assistance in culturing skin fibroblasts, and Dr. Phil Whitfield for the glucocerebroside assay.

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Authors and Affiliations

  1. Lysosomal Diseases Research Unit, A Research Centre of SA Pathology, Women’s and Children’s Hospital, North Adelaide, SA, 5006, Australia

    Litsa Karageorgos & John J. Hopwood

  2. Department of Primary Industries, Attwood, VIC, Australia

    Malcolm J. Lancaster

  3. ASAP Laboratory, Mulgrave, VIC, Australia

    Judith S. Nimmo

Authors
  1. Litsa Karageorgos
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  2. Malcolm J. Lancaster
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  3. Judith S. Nimmo
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  4. John J. Hopwood
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Corresponding author

Correspondence to Litsa Karageorgos.

Additional information

Communicated by: Gregory Pastores

References to electronic databases: Gaucher disease: non-neuronopathic OMIM 230800. Acute neuronopathic OMIM 230900. Subacute neuronopathic OMIM 231000. β-glucocerebrosidase: EC 3.2.1.45. β-glucocerebrosidase HUGO-approved gene symbol: GBA. Human β-glucocerebrosidase gene: OMIM 606463. GenBank/EMBL accession number J03059. Human glucocerebrosidase mRNA: GenBank: M16328. Human β-glucocerebrosidase protein: Swiss-Prot: P04062

Competing interests: None to declare

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Karageorgos, L., Lancaster, M.J., Nimmo, J.S. et al. Gaucher disease in sheep. J Inherit Metab Dis 34, 209–215 (2011). https://doi.org/10.1007/s10545-010-9230-3

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  • DOI: https://doi.org/10.1007/s10545-010-9230-3

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