Human CC10 gene expression in airway epithelium and subchromosomal locus suggest linkage to airway disease

J. G. Hay, C. Danel, C. S. Chu, Ronald Crystal

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Abstract

The CC10 gene encodes the Clara cell 10-kDa protein, which is expressed in airway epithelial cells. Quantification of CC10 gene expression in freshly isolated human proximal airway epithelial cells demonstrated very high mRNA levels, approximately fivefold greater than γ-actin mRNA, and in situ hybridization localized CC10 mRNA to nonciliated airway epithelial cells. Sequence analysis demonstrated that the human CC10 gene is comprised of three short exons separated by a long first and short second intron, and with a 5' flanking region typical of a regulated gene. Three Alu repeats were observed in intron 1 and one in intron 2. Two polymorphic regions within the introns were identified. First, a microsatellite was localized 5' to the third Alu repeat in intron 1 with a variable number of 4- and 5-base pair (bp) repeats and a heterozygosity of 0.71. Second, in 3% of the 168 chromosomes examined, there was the insertion of a human-specific Alu repeat in intron 2, 45 bp 3' to the exon 2-intron junction. In three Centre d'Etude du Polymorphisme Humain families, meiotic breakpoint analysis using these two polymorphic loci localized the CC10 gene to 11 p12-q13 between markers D11S16 and D11S97, a region recently linked to atopy and to the β-subunit of the high-affinity immunoglobulin E receptor. The observations in the present study of high- level expression of the CC10 gene in the epithelium of conducting airways and a subchromosomal localization of the gene to a region potentially linked to inflammatory airway disease, together with the reported anti-inflammatory and immune-modulating properties of the protein, suggest the CC10 gene product may be important in modulating inflammation within the airways. If so, the highly heterozygous microsatellite described in the present study should facilitate analysis of a possible linkage of the CC10 gene with an inherited susceptibility to asthma.

Original languageEnglish
JournalAmerican Journal of Physiology - Lung Cellular and Molecular Physiology
Volume268
Issue number4 12-4
Publication statusPublished - 1 Jan 1995
Externally publishedYes

Fingerprint

Introns
Epithelium
Gene Expression
Genes
Epithelial Cells
Base Pairing
Microsatellite Repeats
Messenger RNA
Exons
IgE Receptors
Chromosomes, Human, Pair 3
5' Flanking Region
In Situ Hybridization
Sequence Analysis
Actins
Proteins
Anti-Inflammatory Agents
Asthma
Inflammation

Keywords

  • Alu family
  • asthma
  • linkage
  • polymorphism

ASJC Scopus subject areas

  • Physiology
  • Pulmonary and Respiratory Medicine
  • Physiology (medical)
  • Cell Biology

Cite this

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title = "Human CC10 gene expression in airway epithelium and subchromosomal locus suggest linkage to airway disease",
abstract = "The CC10 gene encodes the Clara cell 10-kDa protein, which is expressed in airway epithelial cells. Quantification of CC10 gene expression in freshly isolated human proximal airway epithelial cells demonstrated very high mRNA levels, approximately fivefold greater than γ-actin mRNA, and in situ hybridization localized CC10 mRNA to nonciliated airway epithelial cells. Sequence analysis demonstrated that the human CC10 gene is comprised of three short exons separated by a long first and short second intron, and with a 5' flanking region typical of a regulated gene. Three Alu repeats were observed in intron 1 and one in intron 2. Two polymorphic regions within the introns were identified. First, a microsatellite was localized 5' to the third Alu repeat in intron 1 with a variable number of 4- and 5-base pair (bp) repeats and a heterozygosity of 0.71. Second, in 3{\%} of the 168 chromosomes examined, there was the insertion of a human-specific Alu repeat in intron 2, 45 bp 3' to the exon 2-intron junction. In three Centre d'Etude du Polymorphisme Humain families, meiotic breakpoint analysis using these two polymorphic loci localized the CC10 gene to 11 p12-q13 between markers D11S16 and D11S97, a region recently linked to atopy and to the β-subunit of the high-affinity immunoglobulin E receptor. The observations in the present study of high- level expression of the CC10 gene in the epithelium of conducting airways and a subchromosomal localization of the gene to a region potentially linked to inflammatory airway disease, together with the reported anti-inflammatory and immune-modulating properties of the protein, suggest the CC10 gene product may be important in modulating inflammation within the airways. If so, the highly heterozygous microsatellite described in the present study should facilitate analysis of a possible linkage of the CC10 gene with an inherited susceptibility to asthma.",
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N2 - The CC10 gene encodes the Clara cell 10-kDa protein, which is expressed in airway epithelial cells. Quantification of CC10 gene expression in freshly isolated human proximal airway epithelial cells demonstrated very high mRNA levels, approximately fivefold greater than γ-actin mRNA, and in situ hybridization localized CC10 mRNA to nonciliated airway epithelial cells. Sequence analysis demonstrated that the human CC10 gene is comprised of three short exons separated by a long first and short second intron, and with a 5' flanking region typical of a regulated gene. Three Alu repeats were observed in intron 1 and one in intron 2. Two polymorphic regions within the introns were identified. First, a microsatellite was localized 5' to the third Alu repeat in intron 1 with a variable number of 4- and 5-base pair (bp) repeats and a heterozygosity of 0.71. Second, in 3% of the 168 chromosomes examined, there was the insertion of a human-specific Alu repeat in intron 2, 45 bp 3' to the exon 2-intron junction. In three Centre d'Etude du Polymorphisme Humain families, meiotic breakpoint analysis using these two polymorphic loci localized the CC10 gene to 11 p12-q13 between markers D11S16 and D11S97, a region recently linked to atopy and to the β-subunit of the high-affinity immunoglobulin E receptor. The observations in the present study of high- level expression of the CC10 gene in the epithelium of conducting airways and a subchromosomal localization of the gene to a region potentially linked to inflammatory airway disease, together with the reported anti-inflammatory and immune-modulating properties of the protein, suggest the CC10 gene product may be important in modulating inflammation within the airways. If so, the highly heterozygous microsatellite described in the present study should facilitate analysis of a possible linkage of the CC10 gene with an inherited susceptibility to asthma.

AB - The CC10 gene encodes the Clara cell 10-kDa protein, which is expressed in airway epithelial cells. Quantification of CC10 gene expression in freshly isolated human proximal airway epithelial cells demonstrated very high mRNA levels, approximately fivefold greater than γ-actin mRNA, and in situ hybridization localized CC10 mRNA to nonciliated airway epithelial cells. Sequence analysis demonstrated that the human CC10 gene is comprised of three short exons separated by a long first and short second intron, and with a 5' flanking region typical of a regulated gene. Three Alu repeats were observed in intron 1 and one in intron 2. Two polymorphic regions within the introns were identified. First, a microsatellite was localized 5' to the third Alu repeat in intron 1 with a variable number of 4- and 5-base pair (bp) repeats and a heterozygosity of 0.71. Second, in 3% of the 168 chromosomes examined, there was the insertion of a human-specific Alu repeat in intron 2, 45 bp 3' to the exon 2-intron junction. In three Centre d'Etude du Polymorphisme Humain families, meiotic breakpoint analysis using these two polymorphic loci localized the CC10 gene to 11 p12-q13 between markers D11S16 and D11S97, a region recently linked to atopy and to the β-subunit of the high-affinity immunoglobulin E receptor. The observations in the present study of high- level expression of the CC10 gene in the epithelium of conducting airways and a subchromosomal localization of the gene to a region potentially linked to inflammatory airway disease, together with the reported anti-inflammatory and immune-modulating properties of the protein, suggest the CC10 gene product may be important in modulating inflammation within the airways. If so, the highly heterozygous microsatellite described in the present study should facilitate analysis of a possible linkage of the CC10 gene with an inherited susceptibility to asthma.

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