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Structure and chromosomal location of the gene encoding mouse corticosteroid-binding globulin: strain differences in
1Department of Obstetrics and Gynecology, University of Western Ontario, London, Canada.
Gene
|July 8, 1994
Summary
Corticosteroid-binding globulin (CBG) gene structure was analyzed in mice. A specific mutation (Lys201-->Glu) in RIIIS/J mice was found to impair glucocorticoid transport by CBG.
Area of Science:
- Genetics
- Molecular Biology
- Biochemistry
Background:
- Corticosteroid-binding globulin (CBG) is crucial for plasma transport of glucocorticoids.
- CBG belongs to the serine proteinase inhibitor superfamily.
- Understanding CBG gene structure and function is vital for glucocorticoid regulation.
Purpose of the Study:
- To elucidate the gene structure of mouse Corticosteroid-binding globulin (Cbg).
- To identify genetic variations in mouse CBG and their impact on steroid-binding activity.
- To investigate the molecular basis of abnormal CBG function in specific mouse strains.
Main Methods:
- Genomic DNA analysis using lambda EMBL-3 library and PCR amplification.
- Sequencing of Cbg coding regions from different mouse strains.
- Site-directed mutagenesis of Cbg cDNA and expression in MDCK cells.
Main Results:
- Mouse Cbg gene comprises five exons spanning approximately 10.5 kb and is located on chromosome 12.
- Two mutations (Lys201-->Glu and Ala357-->Thr) were identified in RIIIS/J mouse Cbg.
- The Lys201-->Glu substitution was identified as the cause of impaired steroid-binding affinity in RIIIS/J CBG.
Conclusions:
- The study successfully determined the mouse Cbg gene structure and chromosomal localization.
- Genetic variations in CBG can significantly affect glucocorticoid transport.
- The Lys201-->Glu mutation is directly linked to abnormal steroid-binding activity, providing insight into CBG dysfunction.