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Related Experiment Videos

cis and trans elements differ among mouse strains with high and low extrahepatic complement factor B gene expression.

G Garnier1, B Ault, M Kramer

  • 1Department of Pediatrics, Washington University School of Medicine, St. Louis, Missouri 63110.

The Journal of Experimental Medicine
|February 1, 1992
PubMed
Summary

Genetic variations in the Factor B (Bf) gene

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Area of Science:

  • Immunogenetics
  • Molecular Biology
  • Complement System

Background:

  • Factor B (Bf) is a key enzyme in the alternative complement pathway and a major histocompatibility complex (MHC) class III gene.
  • Tissue-specific expression of Bf is crucial for immune regulation.
  • Previous studies identified MHC-associated polymorphisms but lacked detailed mechanistic insights into gene regulation.

Purpose of the Study:

  • To investigate the genetic mechanisms underlying tissue-specific constitutive and regulated expression of the Factor B (Bf) gene.
  • To identify cis-acting DNA sequence variations and trans-acting factors influencing Bf gene expression in different tissues.
  • To explore the potential of Bf regulatory elements as markers for human MHC-associated renal pathology.

Main Methods:

Related Experiment Videos

  • Sequencing of regulatory regions 5' of the mouse Bf gene across different H-2 MHC haplotypes.
  • Assessment of trans-acting factors (DNA-binding nucleoproteins) in liver and kidney tissues.
  • Analysis of nucleotide substitutions and their impact on DNA-protein interactions.
  • Restriction fragment length polymorphism (RFLP) analysis using SmaI and HinfI digestion.

    • Main Results:

    • Significant tissue-specific differences in constitutive Bf expression were observed between mouse haplotypes (e.g., H-2d/u vs. H-2f/z) in kidney and intestine.
    • A point nucleotide substitution near the Bf initiation site was identified, affecting DNA-binding protein interaction and correlating with expression differences.
    • Novel polymorphisms (SmaI and HinfI) were discovered, alongside those linked to known RFLPs.
    • Differences in trans-acting factors were detected in kidney but not liver nucleoproteins between specific mouse strains (B10.PL vs. B10.M).

    Conclusions:

    • Cis-acting sequence variations in the Bf promoter significantly influence tissue-specific gene expression.
    • Trans-acting factors also contribute to differential Bf regulation, particularly in the kidney.
    • High homology between human and mouse Bf regulatory regions suggests potential for Bf promoter polymorphisms to serve as markers for human MHC-associated renal diseases.