alexa Viable mouse models of acid beta-glucosidase deficiency: the defect in Gaucher disease.
Bioinformatics & Systems Biology

Bioinformatics & Systems Biology

Journal of Glycomics & Lipidomics

Author(s): Xu YH, Quinn B, Witte D, Grabowski GA

Abstract Share this page

Abstract Gaucher disease is an autosomal recessively inherited disease caused by mutations at the acid beta-glucosidase (GCase) locus (GBA). To develop viable models of Gaucher disease, point mutations (pmuts), encoding N370S, V394L, D409H, or D409V were introduced into the mouse GCase (gba) locus. DNA sequencing verified each unique pmut. Mutant GCase mRNAs were near wild-type (WT) levels. GCase activities were reduced to 2 to 25\% of WT in liver, lung, spleen, and cultured fibroblasts from pmut/pmut or pmut/null mice. The corresponding brain GCase activities were approximately 25\% of WT. N370S homozygosity was lethal in the neonatal period. For the other pmut mice, a few storage cells appeared in the spleen at > or =7 months (D409H or D409V homozygotes) or > or =1 year (V394L homozygotes). V394L/null, D409H/null, or D409V/null mice showed scattered storage cells in spleen at approximately 3 to 4 months. Occasional storage cells (sinusoidal cells) were present in liver. In D409V/null mice, large numbers of Mac-3-positive storage cells (ie, macrophages) accumulated in the lung. Glycosphingolipid analyses showed varying rates of progressive glucosylceramide accumulation in visceral organs of pmut/pmut or pmut/null mice, but not in brain. These GCase-deficient mice provide tools for gaining insight into the pathophysiology of Gaucher disease and developing improved therapies.
This article was published in Am J Pathol and referenced in Journal of Glycomics & Lipidomics

Relevant Expert PPTs

Relevant Speaker PPTs

Recommended Conferences

Relevant Topics

Peer Reviewed Journals
 
Make the best use of Scientific Research and information from our 700 + peer reviewed, Open Access Journals
International Conferences 2017-18
 
Meet Inspiring Speakers and Experts at our 3000+ Global Annual Meetings

Contact Us

 
© 2008-2017 OMICS International - Open Access Publisher. Best viewed in Mozilla Firefox | Google Chrome | Above IE 7.0 version
adwords