These Scnn1b-transgenic mice exhibit airway obstruction with mucus, neutrophilic inflammation, goblet cell metaplasia and mucus hypersecretion; similar to the clinical and pathologic descriptions of early cystic fibrosis lung disease.
Wanda K. O'Neal, Univ. of North Carolina at Chapel Hill
Genetic Background | Generation |
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Allele Type |
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Transgenic (Inserted expressed sequence) |
These Scnn1b-transgenic mice overexpress the mouse nonvoltage-gated 1 beta, Scnn1b, under the direction of the rat secretoglobin, family 1A, member 1 (uteroglobin; Clara cell secretory protein) promoter. Approximately 40-60% of hemizygous mice die between birth and 4 weeks of age due to airway obstruction asphyxia. While the donating investigator reports that most hemizygous transgenic mice (80-90%) on the congenic C57BL/6N background (Stock No. 030949) survive past postnatal day 14, hemizygous mice on the congenic C57BL/6J (Stock No. 006438), B6;C3H mixed (Stock No. 005315), and B6C3Fe hybrid (Stock No. 006176) backgrounds at The Jackson Laboratory exhibit an approximately 40% survival rate to weaning age. Histological analysis reveals that mucus accumulation, plaques and plugs in airways occur postnatally. Basal and amiloride-sensitive short-circuit currents in tracheal tissue are increased. Airway surface liquid (ASL) volume, mucus transport and clearance are reduced. Bronchial lavage and histological analysis shows mutant mice exhibit characteristics of cystic fibrosis lung disease including chronic bronchitis, airway inflammation, airway lumen infiltration of macrophage and neutrophils, and goblet cell metaplasia. These Scnn1b-transgenic mice may be useful in studies of cystic fibrosis, and are available on different genetic backgrounds such as B6;C3H mixed (Stock No. 005315), B6C3Fe hybrid (Stock No. 006176), C57BL6-congenic (Stock No. 006438), and congenic C57BL/6N (Stock No. 030949).
Importation of this model was supported by The Boomer Esiason Foundation.
A transgenic construct containing the protein coding region of the mouse sodium channel, nonvoltage-gated 1 beta gene (Scnn1b) under the control of the rat secretoglobin, family 1A, member 1 (uteroglobin), Scgb1a1, promoter and SV40 polyadenylation site sequence was injected into fertilized B6C3F1 donor eggs. Founder line 6608 was established.
Expressed Gene | Scnn1b, sodium channel, nonvoltage-gated 1 beta, mouse, laboratory |
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Site of Expression |
Allele Name | transgene insertion 6608, Richard Boucher |
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Allele Type | Transgenic (Inserted expressed sequence) |
Allele Synonym(s) | betaENaC-Tg |
Gene Symbol and Name | Tg(Scgb1a1-Scnn1b)6608Bouc, transgene insertion 6608, Richard Boucher |
Gene Synonym(s) | |
Promoter | Scgb1a1, secretoglobin family 1A member 1, rat |
Expressed Gene | Scnn1b, sodium channel, nonvoltage-gated 1 beta, mouse, laboratory |
Strain of Origin | (C3H x C57BL/6)F1 |
Chromosome | 5 |
General Note | A second transgenic line, Tg(Scgb1a1-Scnn1b)6047Bouc, was created in the same genetic background. The phenotypes of the two lines are indistinguishable. Complete histological examination of multiple organs and systems reveals no pathology of organs other than lungs of transgenic mice. |
Molecular Note | Approximately 2330 base pairs of 5' flanking sequence from the rat airway-specific Scgb1a1 (also called the Clara cell secretory protein) gene were inserted into the pTG1 vector upstream of exon 1 (104 base pairs, including the transcription initiation site), intron 1 (947 base pairs) and 10 base pairs of exon 2 from the mouse transthyretin gene; the protein-coding region of the mouse Scnn1b cDNA, inserted just downstream of the transthyretin exon 2 splice acceptor, is followed by the SV40 early-region polyadenylation signal. In situ hybridization with a transgene-specific antisense probe confirmed expression in airway epithelia of the lung. The insertion site was identified by in situ hybridization; it is located on chromosome 5 near the B-C1 chromosome band junction. |
Mutations Made By | Wanda O'Neal, Univ. of North Carolina at Chapel Hill |
When maintaining a live colony, hemizygous mice are bred to B6C3F1/J (Stock No. 100010; an F1 strain with the desired functional Tlr4 allele from the C57BL/6J background). Hemizygous mice at The Jackson Laboratory exhibit an approximately 40% survival rate to weaning age.
When using the Scnn1b-transgenic mouse strain in a publication, please cite the originating article(s) and include JAX stock #005315 in your Materials and Methods section.
Facility Barrier Level Descriptions
Service/Product | Description | Price |
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Hemizygous or Non carrier for Tg(Scgb1a1-Scnn1b)6608Bouc |
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