Inherited complement C3 deficiency

Reduced C3 mRNA and protein levels in a Laotian kindred

Lori Singer, Michelle L. Van Hee, Marja Liisa Lokki, J. Krámer, Michael S. Borzy, Rick A. Wetsel

Research output: Contribution to journalArticle

10 Citations (Scopus)

Abstract

To determine the molecular basis of complement C3 deficiency in a Laotian kindred, the homozygous C3-deficient male propositus was studied. By ELISA, this individual's serum was determined to contain approximately 4 μg/ml C3 (0.3% of normal). In accord with this result, anti-C3 immunoprecipitation of [35S]-methionine-labeled fibroblasts from this C3D individual revealed pro-C3 of normal size (180,000 M(r)), but in significantly reduced amounts (~1% of normal fibroblasts), that was processed and secreted with normal-size α- and β-chains. In addition, C3-specific mRNA of normal size (5.2 kb) but in reduced quantity (~1% of normal) was detected in this individual's fibroblasts by Northern analysis. The nucleotide sequence of the transcriptional initiation site, the promoter, and the IL-1β/IL-6 cis-regulatory elements of the C3-deficient gene are normal in this C3-deficient individual, indicating that the low C3 mRNA and protein levels are not caused by reduced C3 transcription that is the result of a cis-mutation. Moreover, cDNA sequencing studies revealed no defect in the C3-deficient mRNA, including the areas mutated in four previously characterized C3-deficient patients. These data indicate that (1) C3 protein deficieney in this Laotian patient results from reduced levels of C3-specific mRNA, (2) the small amount of expressed C3 protein is processed and secreted normally from the deficient cells, and (3) the molecular genetic defect(s), although not yet delineated, is different from those described in other C3-deficient individuals, thereby providing additional evidence for numerous mutations that cause inherited C3 deficiency in humans.

Original languageEnglish
Pages (from-to)244-252
Number of pages9
JournalClinical Immunology and Immunopathology
Volume81
Issue number3
DOIs
Publication statusPublished - Dec 1996

Fingerprint

Complement C3
Messenger RNA
Fibroblasts
Proteins
Mutation
Interleukin-1
Immunoprecipitation
Methionine
Molecular Biology
Interleukin-6
Complementary DNA
Enzyme-Linked Immunosorbent Assay
Serum
Genes

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Pathology and Forensic Medicine

Cite this

Inherited complement C3 deficiency : Reduced C3 mRNA and protein levels in a Laotian kindred. / Singer, Lori; Van Hee, Michelle L.; Lokki, Marja Liisa; Krámer, J.; Borzy, Michael S.; Wetsel, Rick A.

In: Clinical Immunology and Immunopathology, Vol. 81, No. 3, 12.1996, p. 244-252.

Research output: Contribution to journalArticle

Singer, Lori ; Van Hee, Michelle L. ; Lokki, Marja Liisa ; Krámer, J. ; Borzy, Michael S. ; Wetsel, Rick A. / Inherited complement C3 deficiency : Reduced C3 mRNA and protein levels in a Laotian kindred. In: Clinical Immunology and Immunopathology. 1996 ; Vol. 81, No. 3. pp. 244-252.
@article{0cb43014c73641bca25db16c3532a02e,
title = "Inherited complement C3 deficiency: Reduced C3 mRNA and protein levels in a Laotian kindred",
abstract = "To determine the molecular basis of complement C3 deficiency in a Laotian kindred, the homozygous C3-deficient male propositus was studied. By ELISA, this individual's serum was determined to contain approximately 4 μg/ml C3 (0.3{\%} of normal). In accord with this result, anti-C3 immunoprecipitation of [35S]-methionine-labeled fibroblasts from this C3D individual revealed pro-C3 of normal size (180,000 M(r)), but in significantly reduced amounts (~1{\%} of normal fibroblasts), that was processed and secreted with normal-size α- and β-chains. In addition, C3-specific mRNA of normal size (5.2 kb) but in reduced quantity (~1{\%} of normal) was detected in this individual's fibroblasts by Northern analysis. The nucleotide sequence of the transcriptional initiation site, the promoter, and the IL-1β/IL-6 cis-regulatory elements of the C3-deficient gene are normal in this C3-deficient individual, indicating that the low C3 mRNA and protein levels are not caused by reduced C3 transcription that is the result of a cis-mutation. Moreover, cDNA sequencing studies revealed no defect in the C3-deficient mRNA, including the areas mutated in four previously characterized C3-deficient patients. These data indicate that (1) C3 protein deficieney in this Laotian patient results from reduced levels of C3-specific mRNA, (2) the small amount of expressed C3 protein is processed and secreted normally from the deficient cells, and (3) the molecular genetic defect(s), although not yet delineated, is different from those described in other C3-deficient individuals, thereby providing additional evidence for numerous mutations that cause inherited C3 deficiency in humans.",
author = "Lori Singer and {Van Hee}, {Michelle L.} and Lokki, {Marja Liisa} and J. Kr{\'a}mer and Borzy, {Michael S.} and Wetsel, {Rick A.}",
year = "1996",
month = "12",
doi = "10.1006/clin.1996.0185",
language = "English",
volume = "81",
pages = "244--252",
journal = "Clinical Immunology",
issn = "1521-6616",
publisher = "Academic Press Inc.",
number = "3",

}

TY - JOUR

T1 - Inherited complement C3 deficiency

T2 - Reduced C3 mRNA and protein levels in a Laotian kindred

AU - Singer, Lori

AU - Van Hee, Michelle L.

AU - Lokki, Marja Liisa

AU - Krámer, J.

AU - Borzy, Michael S.

AU - Wetsel, Rick A.

PY - 1996/12

Y1 - 1996/12

N2 - To determine the molecular basis of complement C3 deficiency in a Laotian kindred, the homozygous C3-deficient male propositus was studied. By ELISA, this individual's serum was determined to contain approximately 4 μg/ml C3 (0.3% of normal). In accord with this result, anti-C3 immunoprecipitation of [35S]-methionine-labeled fibroblasts from this C3D individual revealed pro-C3 of normal size (180,000 M(r)), but in significantly reduced amounts (~1% of normal fibroblasts), that was processed and secreted with normal-size α- and β-chains. In addition, C3-specific mRNA of normal size (5.2 kb) but in reduced quantity (~1% of normal) was detected in this individual's fibroblasts by Northern analysis. The nucleotide sequence of the transcriptional initiation site, the promoter, and the IL-1β/IL-6 cis-regulatory elements of the C3-deficient gene are normal in this C3-deficient individual, indicating that the low C3 mRNA and protein levels are not caused by reduced C3 transcription that is the result of a cis-mutation. Moreover, cDNA sequencing studies revealed no defect in the C3-deficient mRNA, including the areas mutated in four previously characterized C3-deficient patients. These data indicate that (1) C3 protein deficieney in this Laotian patient results from reduced levels of C3-specific mRNA, (2) the small amount of expressed C3 protein is processed and secreted normally from the deficient cells, and (3) the molecular genetic defect(s), although not yet delineated, is different from those described in other C3-deficient individuals, thereby providing additional evidence for numerous mutations that cause inherited C3 deficiency in humans.

AB - To determine the molecular basis of complement C3 deficiency in a Laotian kindred, the homozygous C3-deficient male propositus was studied. By ELISA, this individual's serum was determined to contain approximately 4 μg/ml C3 (0.3% of normal). In accord with this result, anti-C3 immunoprecipitation of [35S]-methionine-labeled fibroblasts from this C3D individual revealed pro-C3 of normal size (180,000 M(r)), but in significantly reduced amounts (~1% of normal fibroblasts), that was processed and secreted with normal-size α- and β-chains. In addition, C3-specific mRNA of normal size (5.2 kb) but in reduced quantity (~1% of normal) was detected in this individual's fibroblasts by Northern analysis. The nucleotide sequence of the transcriptional initiation site, the promoter, and the IL-1β/IL-6 cis-regulatory elements of the C3-deficient gene are normal in this C3-deficient individual, indicating that the low C3 mRNA and protein levels are not caused by reduced C3 transcription that is the result of a cis-mutation. Moreover, cDNA sequencing studies revealed no defect in the C3-deficient mRNA, including the areas mutated in four previously characterized C3-deficient patients. These data indicate that (1) C3 protein deficieney in this Laotian patient results from reduced levels of C3-specific mRNA, (2) the small amount of expressed C3 protein is processed and secreted normally from the deficient cells, and (3) the molecular genetic defect(s), although not yet delineated, is different from those described in other C3-deficient individuals, thereby providing additional evidence for numerous mutations that cause inherited C3 deficiency in humans.

UR - http://www.scopus.com/inward/record.url?scp=0030561159&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0030561159&partnerID=8YFLogxK

U2 - 10.1006/clin.1996.0185

DO - 10.1006/clin.1996.0185

M3 - Article

VL - 81

SP - 244

EP - 252

JO - Clinical Immunology

JF - Clinical Immunology

SN - 1521-6616

IS - 3

ER -