Murine Submucosal Glands Are Clonally Derived and Show a Cystic Fibrosis Gene-Dependent Distribution Pattern

Submucosal glands (SMGs) are the major site of expression of the cystic fibrosis (CF) transmembrane conductance regulator gene (CFTR) in the human lung. As such, SMGs may be a critical component of CF lung disease pathogenesis and an important target for gene therapy. Gene-targeted mouse models exis...

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Vydané v:American journal of respiratory cell and molecular biology Ročník 20; číslo 6; s. 1181 - 1189
Hlavní autori: Borthwick, Duncan W, West, John D, Keighren, Margaret A, Flockhart, Jean H, Innes, Brendan A, Dorin, Julia R
Médium: Journal Article
Jazyk:English
Vydavateľské údaje: United States Am Thoracic Soc 01.06.1999
American Thoracic Society
Predmet:
Animals
Clone Cells
Cystic Fibrosis Transmembrane Conductance Regulator - metabolism
Humans
Mice
Mice, Inbred Strains
Mice, Transgenic
Models, Genetic
Mucous Membrane - metabolism
Mucous Membrane - physiology
Mucus - secretion
Muramidase - biosynthesis
Serous Membrane - metabolism
Stem Cells - metabolism
Trachea - anatomy & histology
Trachea - metabolism
Transplantation Chimera
ISSN:1044-1549, 1535-4989
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Shrnutí:Submucosal glands (SMGs) are the major site of expression of the cystic fibrosis (CF) transmembrane conductance regulator gene (CFTR) in the human lung. As such, SMGs may be a critical component of CF lung disease pathogenesis and an important target for gene therapy. Gene-targeted mouse models exist for CF and these are used to validate gene therapy or other interventions and to dissect CF phenotypes. It is important, therefore, to compare human and mouse SMGs. We show that SMGs in the mouse are similar in structure, cell types, and Cftr expression to those in the human. Murine SMGs were found to be present in the proximal regions of the trachea at the same density as in humans but, unlike in humans, did not extend below the trachea. Upon investigation of homozygous Cftr tm1HGU and Cftr tm1G551D mutant mice, SMGs were found to extend more distally than those in wild-type control mice (P < 0.05). To investigate the development of SMGs we generated aggregation chimeric mice. Chimeric offspring contained a contribution of transgenic cells that were detectable either by DNA in situ hybridization (reiterated beta-globin transgene TgN[Hbb-bl]83Clo) or beta-galactosidase histochemistry (Lac Z reporter gene TgR[ROSA26]- 26Sor). Analysis of the distribution of transgenic cells in chimeric SMGs suggests that SMGs are clonally derived.
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ISSN:1044-1549
1535-4989
DOI:10.1165/ajrcmb.20.6.3475