title: The molecular basis for genetic deficiency of the second component of human complement.
abstract: Genetic deficiency of the second component of complement (C2) is the most common complement-deficiency state among Western Europeans and is frequently associated with autoimmune diseases. To examine the molecular basis of this deficiency, we established cultures of blood monocytes from four families with C2-deficient members. Using a hemolytic-plaque assay, [35S]methionine metabolic labeling of proteins in tissue culture and immunoprecipitation, RNA extraction and Northern blot analysis, and DNA restriction-enzyme digestion and Southern blot analysis, we found that C2 deficiency is not due to a major gene deletion or rearrangement but is the result of a specific and selective pretranslational regulatory defect in C2 gene expression. This leads to a lack of detectable C2 mRNA and a lack of synthesis of C2 protein. The approach used in this study should prove useful in examination of other plasma protein deficiencies, especially those in which the deficient gene is normally expressed in peripheral-blood monocytes or tissue macrophages and in which ethical considerations preclude the use of liver or other tissue for study.
authors.forename: F S
authors.initials: FS
authors.lastname: Cole
authors.forename: A S
authors.initials: AS
authors.lastname: Whitehead
authors.forename: H S
authors.initials: HS
authors.lastname: Auerbach
authors.forename: T
authors.initials: T
authors.lastname: Lint
authors.forename: H J
authors.initials: HJ
authors.lastname: Zeitz
authors.forename: P
authors.initials: P
authors.lastname: Kilbridge
authors.forename: H R
authors.initials: HR
authors.lastname: Colten
mesh_terms: D001327:Autoimmune Diseases / Q000235:genetics; D002478:Cells, Cultured; D003175:Complement C2 / Q000172:deficiency* / Q000235:genetics; D004247:DNA / Q000032:analysis; D004262:DNA Restriction Enzymes / Q000494:pharmacology; D004591:Electrophoresis, Polyacrylamide Gel; D005786:Gene Expression Regulation; D006462:Hemolytic Plaque Technique; D006801:Humans; D008715:Methionine / Q000378:metabolism; D009000:Monocytes / Q000378:metabolism; D012313:RNA / Q000032:analysis; D012333:RNA, Messenger / Q000032:analysis; D013462:Sulfur Radioisotopes
chemical_list: D003175:Complement C2; D012333:RNA, Messenger; D013462:Sulfur Radioisotopes; D012313:RNA; D004247:DNA; D008715:Methionine; D004262:DNA Restriction Enzymes