Conditional expression of human acid beta-glucosidase improves the visceral phenotype in a Gaucher disease mouse model.

Conditional expression of human acid beta-glucosidase improves the visceral phenotype in a Gaucher disease mouse model. Research Abstract Details 

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Conditional expression of human acid beta-glucosidase improves the visceral phenotype in a Gaucher disease mouse model. Abstract Text:

Ying Sun,Brian Quinn,You-Hai Xu,Tatyana Leonova,David P Witte,Gregory A Grabowski,

The reversibility and regression of histological and biochemical findings in a mouse model of Gaucher disease (4L/PS-NA) was evaluated using a liver-enriched activator protein promoter control of a tetracycline-controlled transcriptional activation-responsive human acid beta-glucosidase (hGCase) transgenic system. 4L/PS-NA has the acid beta-glucosidase (GCase) V394L/V394L (4L) point mutation combined with hypomorphic ( approximately 6% wild-type) expression of the mouse prosaposin transgene (PS-NA). The hGCase/4L/PS-NA had exclusive liver expression of hGCase controlled by doxycycline (DOX). In the absence of DOX, hGCase was secreted from liver at levels of approximately 120 microg/ml serum with only approximately 8% of full activity, following exposure to pH 7.4 in serum. The hGCase activity and protein were detected in cells of the liver (massive), lung, and spleen, but not the brain. The visceral tissue storage cells and glucosylceramide (GC) accumulation in hGCase/4L/PS-NA were decreased from that in 4L/PS-NA mice. Turning off hGCase expression with dietary DOX led to reaccumulation of storage cells and of GC in liver, lung, and spleen, and macrophage activation in those tissues. This study demonstrates that conditionally expressed hGCase supplemented the existing mutant mouse GCase to control visceral substrate accumulation in vivo.

Conditional expression of human acid beta-glucosidase improves the visceral phenotype in a Gaucher disease mouse model. Publishing Authors By Initials

Y Sun,B Quinn,YH Xu,T Leonova,DP Witte,GA Grabowski,

For similar body regions: viscera research abstracts see: body regions: viscera research

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Conditional expression of human acid beta-glucosidase improves the visceral phenotype in a Gaucher disease mouse model. Journal Published:

PUBLICATION TYPE: Research Support, N.I.H., Extr

Journal: Journal of lipid research

VOLUME: 47

Page Numbers: 2161-70

Journal Abbreviation: J. Lipid Res.

ISSN: 0022-2275

DAY: 21

MONTH: 07

YEAR: 2006

Conditional expression of human acid beta-glucosidase improves the visceral phenotype in a Gaucher disease mouse model. Information

Number of References:

LANGUAGE: eng

NlmUniqueID: 376606

Conditional expression of human acid beta-glucosidase improves the visceral phenotype in a Gaucher disease mouse model. Keywords Mesh Terms:

KEYWORDS: Viscera

MESH TERMS: pathology

Chemical & Substance for Abstract: Conditional expression of human acid beta-glucosidase improves the visceral phenotype in a Gaucher disease mouse model. Information

Substance Name: Glucosylceramidase

Registry Number: EC 3.2.1.45

Grant and Affiliation Information for Conditional expression of human acid beta-glucosidase improves the visceral phenotype in a Gaucher disease mouse model.

AFFILIATION: Division of Human Genetics, Children's Hospital Research Foundation and University of Cincinnati College of Medicine, Department of Pediatrics, Cincinnati, OH 45229-3039, USA.

Country: United States

AGENCY: United States NINDS

GRANT: NS-36681

ACRONYM: NS

MEDLINETA: J Lipid Res

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