B6C3Fe-Tg(Scgb1a1-Scnn1b)6608Bouc/J

Stock number: 006176
Product name: Scnn1b-Tg
Research areas: Developmental Biology Research, Immunology, Inflammation and Autoimmunity Research, Internal/Organ Research

Description

These transgenic mice exhibit dehydrated mucosal surfaces of the airways, producing mucus obstruction, inflammation, and neonatal mortality.

Detailed description

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. While the donating investigator reports that most hemizygous transgenic mice (80-90%) on the congenic C57BL/6N background (Stock No. 30949) 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. Hemizygous mice that do not survive die due to airway obstruction asphyxia. Mice exhibit chronic inflammation with neutrophil infiltration, chronic mucus hypersecretion and emphysema. 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).

In an attempt to offer alleles on well-characterized or multiple genetic backgrounds, alleles are frequently moved to a genetic background different from that on which an allele was first characterized. This is the case for the strain above. It should be noted that the phenotype could vary from that originally described. We will modify the strain description if necessary as published results become available.

Importation of this model was supported by The Boomer Esiason Foundation.

Development

A transgenic construct containing the mouse sodium channel, nonvoltage-gated 1 beta coding sequence (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 mice (line 6608) was subsequently established and bred B6C3FeF1/J a/a (Stock No. 001022) for 5 generations prior to arrival at The Jackson Laboratory.

Allele

Symbol: Tg(Scgb1a1-Scnn1b)6608Bouc
Name: transgene insertion 6608, Richard Boucher
MGI accession ID: MGI:3605471
Generation method: Transgenic
Attributes: Inserted expressed sequence
Synonyms: betaENaC-Tg
Marker symbol: Tg(Scgb1a1-Scnn1b)6608Bouc
Marker name: transgene insertion 6608, Richard Boucher
Chromosome: 5
Strain of origin: (C3H x C57BL/6)F1
Expressed genes: Scnn1b,sodium channel, nonvoltage-gated 1 beta,mouse, laboratory
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.
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.