• Register
X
Forgot Password

If you have forgotten your password you can enter your email here and get a temporary password sent to your email.

X

Leaving Community

Are you sure you want to leave this community? Leaving the community will revoke any permissions you have been granted in this community.

No
Yes

Targeted disruption of the mouse lysosomal acid lipase gene: long-term survival with massive cholesteryl ester and triglyceride storage.

Lysosomal acid lipase (LAL) is essential for the hydrolysis of the triglycerides and cholesteryl esters in lysosomes. Its deficiency produces two phenotypes, a severe infantile-onset variant, Wolman disease (WD), and a later onset variant, cholesteryl ester storage disease (CESD). A mouse model with a LAL null mutation was produced by targeting disruption of the mouse gene. Homozygote knockout mice (lal -/lal-) produce no LAL mRNA, protein or enzyme activity. The lal-/lal- mice are born in Mendelian ratios, are normal appearing at birth, and follow normal development into adulthood. However, massive accumulation of triglycerides and cholesteryl esters occurs in several organs. By 21 days, the liver develops a yellow-orange color and is approximately 1.5-2.0x larger than normal. The accumulated cholesteryl esters and triglycerides are approximately 30-fold greater than normal. The lal+/lal- mice have approximately 50% of normal LAL activity and do not show lipid accumulation. Male and female lal-/lal- mice are fertile and can be bred to produce progeny. This mouse model is a phenotypic model of human CESD, and a biochemical and histopathologic mimic of human WD. The lal-/lal- mice provide a model to determine the role of LAL in lipid metabolism and the pathogenesis of its deficiency states.

Pubmed ID: 9700186

Authors

  • Du H
  • Duanmu M
  • Witte D
  • Grabowski GA

Journal

Human molecular genetics

Publication Data

September 16, 1998

Associated Grants

  • Agency: NIDDK NIH HHS, Id: DK 36729

Mesh Terms

  • Animals
  • Base Sequence
  • Cholesterol Ester Storage Disease
  • DNA Primers
  • Disease Models, Animal
  • Female
  • Gene Targeting
  • Humans
  • Infant
  • Lipase
  • Liver
  • Lysosomes
  • Male
  • Mice
  • Mice, Knockout
  • Phenotype
  • Spleen
  • Triglycerides
  • Wolman Disease