Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Query: KEGG:D03345 (
beta-Galactosidase
)
434
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
Mice with overexpressed cardiac
Gsalpha
develop cardiomyopathy, characterized by myocyte hypertrophy and extensive myocardial fibrosis. The cardiomyopathy likely involves chronically enhanced beta-adrenergic signaling, because it can be blocked with long-term propranolol treatment. It remains unknown whether the genotype of the myocyte is solely responsible for the progressive pathological changes. A chimeric population in the heart should answer this question. Accordingly, we developed a chimeric animal, which combined cells from a transgenic overexpressed
Gsalpha
parent and a Rosa mouse containing the LacZ reporter gene, facilitating identification of the non-
Gsalpha
cells, which express a blue color with exposure to beta-galactosidase. We studied these animals at 14 to 17 months of age (when cardiomyopathy should have been present), with the proportion of
Gsalpha
cells in the myocardium ranging from 5% to 88%.
beta-Galactosidase
staining of the hearts demonstrated
Gsalpha
and Rosa cells, exhibiting a mosaic pattern. The fibrosis and hypertrophy, characteristic of the cardiomyopathy, were not distributed randomly. There was a direct correlation (r=0.85) between the extent of myocyte hypertrophy (determined by computer imaging) and the quantity of
Gsalpha
cells. The fibrosis, determined by picric acid Sirius red, was also more prominent in areas with the greatest
Gsalpha
cell density, with a correlation of r=0.88. Thus, the overexpressed
Gsalpha
can exert its action over the life of the animal, resulting in a local picture of cardiomyopathic damage in discrete regions of the heart, where clusters of the overexpressed
Gsalpha
cells reside, sparing the clusters of normal cells derived from the normal Rosa parent.
...
PMID:Determinants of the cardiomyopathic phenotype in chimeric mice overexpressing cardiac Gsalpha. 1076 15