TY - JOUR
T1 - Gaucher disease in sheep
AU - Karageorgos, Litsa
AU - Lancaster, Malcolm J.
AU - Nimmo, Judith S.
AU - Hopwood, John J.
N1 - Funding Information:
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.
PY - 2011/2
Y1 - 2011/2
N2 - 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.
AB - 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.
UR - https://www.scopus.com/pages/publications/79955792707
U2 - 10.1007/s10545-010-9230-3
DO - 10.1007/s10545-010-9230-3
M3 - Article
C2 - 20978939
AN - SCOPUS:79955792707
SN - 0141-8955
VL - 34
SP - 209
EP - 215
JO - Journal of Inherited Metabolic Disease
JF - Journal of Inherited Metabolic Disease
IS - 1
ER -