Overview

Also Known As:Scnn1b-Tg

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

Donating Investigator

IMR Colony, The Jackson Laboratory

Genetic overview

Genetic Background	Generation

Tg(Scgb1a1-Scnn1b)6608Bouc

Allele Type
Transgenic (Inserted expressed sequence)

View Genetics

Research Applications

Developmental Biology Research
Immunology, Inflammation and Autoimmunity Research
Internal/Organ Research

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Base Price

Starting at:

$2,854.50 Domestic price Cryo Recovery

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Details

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.

Expression Data

Expressed Gene	Scnn1b, sodium channel, nonvoltage-gated 1 beta, mouse, laboratory
Site of Expression

Control Suggestions

Noncarrier

Approximate Controls

001022 B6C3FeF1/J a/a

Additional Information

Considerations for Choosing Controls

Selected References

Hackett BP; Gitlin JD. 1992. Cell-specific expression of a Clara cell secretory protein-human growth hormone gene in the bronchiolar epithelium of transgenic mice. Proc Natl Acad Sci U S A 89(19):9079-83PubMed: 1409605 MGI: J:101823
Mall M; Grubb BR; Harkema JR; O'Neal WK; Boucher RC. 2004. Increased airway epithelial Na+ absorption produces cystic fibrosis-like lung disease in mice. Nat Med 10(5):487-93PubMed: 15077107 MGI: J:91139
Ostrowski LE; Hutchins JR; Zakel K; O'Neal WK. 2003. Targeting expression of a transgene to the airway surface epithelium using a ciliated cell-specific promoter. Mol Ther 8(4):637-45PubMed: 14529837 MGI: J:101822

View All References

Genetics

Tg(Scgb1a1-Scnn1b)6608Bouc

Allele Symbol: Tg(Scgb1a1-Scnn1b)6608Bouc

Allele Name	transgene insertion 6608, Richard Boucher
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

Disease/Phenotype

Disease Terms

Characteristics of this human disease are associated with transgenes and other mutation types in the mouse.

cystic fibrosis

Research Areas By Phenotype

This mouse can be used to support research in many areas including:

Developmental Biology Research
- Internal/Organ Defects
  - lung
Immunology, Inflammation and Autoimmunity Research
- Cystic Fibrosis
Internal/Organ Research
- Lung Defects

Mammalian Phenotype Terms by Genotype

The following phenotype information is associated with a similar, but not exact match to this JAX^® Mice strain

Genotype: Tg(Scgb1a1-Scnn1b)6608Bouc/0
B6.Cg-Tg(Scgb1a1-Scnn1b)6608Bouc

cellular phenotype

pulmonary epithelial necrosis
- extent of airway necrosis in 3 week old mice does not differ on the BALB/c or C57BL/6 background
- Background Sensitivity - increase in the number of necrotic cells in the airway epithelium, however the level of necrosis is less on the C57BL/6 background compared to the BALB/c background in neonates

immune system phenotype

respiratory system inflammation
- airway inflammation, with similar levels on the C57BL/6 or BALB/c backgrounds

mortality/aging

postnatal lethality, incomplete penetrance
- Background Sensitivity - around 14% of mice die due to airway mucus obstruction, indicating reduced mortality on the C57BL/6 background compared to a mixed C3H and C57BL/6 or BALB/c congenic background

respiratory system phenotype

abnormal mucociliary clearance
- however, extent of airway mucus obstruction in 3 week old mice does not differ on the C57BL/6 and the BALB/c backgrounds
- Background Sensitivity - mucus obstruction is seen in the trachea but not in the intrapulmonary airways of neonates, with mucus content increased to a lesser extent on the C57BL/6 background compared to the BALB/c background

abnormal respiratory mucosa goblet cell morphology
- extent of goblet cell metaplasia is similar on the C57BL/6 and the BALB/c backgrounds

abnormal respiratory system physiology
- cAMP-induced short-circuit current is increased in neonatal tracheal tissue
- increase in basal and amiloride-sensitive short-circuit current in neonatal tracheal tissue, indicating increased airway absorption of Na⁺

emphysema
- extent of emphysema formation in 3 week old mice does not differ on the C57BL/6 or BALB/c backgrounds

pulmonary epithelial necrosis
- extent of airway necrosis in 3 week old mice does not differ on the BALB/c or C57BL/6 background
- Background Sensitivity - increase in the number of necrotic cells in the airway epithelium, however the level of necrosis is less on the C57BL/6 background compared to the BALB/c background in neonates

respiratory system inflammation
- airway inflammation, with similar levels on the C57BL/6 or BALB/c backgrounds

Genotype: Tg(Scgb1a1-Scnn1b)6608Bouc/0
C.Cg-Tg(Scgb1a1-Scnn1b)6608Bouc

cellular phenotype

pulmonary epithelial necrosis
- extent of airway necrosis in 3 week old mice does not differ on the BALB/c or C57BL/6 background
- Background Sensitivity - the number of necrotic cells in the airway epithelium is increased, with a greater increase on the BALB/c background compared to the C57BL/6 background in neonates

immune system phenotype

respiratory system inflammation
- airway inflammation, with similar levels on the C57BL/6 or BALB/c backgrounds

mortality/aging

postnatal lethality, incomplete penetrance
- Background Sensitivity - 81% of mice die due to airway mucus obstruction, indicating increased mortality on the BALB/c background compared to a mixed C3H and C57BL/6 or C57BL/6 congenic background

respiratory system phenotype

abnormal mucociliary clearance
- extent of airway mucous obstruction in 3 week old mice does not differ on the BALB/c or C57BL/6 background
- Background Sensitivity - mucus obstruction is seen in the trachea but not in the intrapulmonary airways of neonates, with mucus content increased to a greater extent on the BALB/c background compared to the C57BL/6 background

abnormal respiratory mucosa goblet cell morphology
- extent of goblet cell metaplasia is similar on the C57BL/6 and the BALB/c background

abnormal respiratory system physiology
- Background Sensitivity - bumetanide-sensitive and CFTR_inh-172-sensitive short-circuit current is decreased in tracheal tissues of neonates on the BALB/c background compared to on the C57BL/6 background, indicating that basal chloride secretion is lower on the BALB/c background
- cAMP-induced short-circuit current is increased in neonatal tracheal tissue
- Background Sensitivity - ckground
- increase in basal and amiloride-sensitive short-circuit current in neonatal tracheal tissue, indicating increased airway absorption of Na⁺

emphysema
- extent of emphysema formation in 3 week old mice does not differ on the C57BL/6 or BALB/c background

pulmonary epithelial necrosis
- extent of airway necrosis in 3 week old mice does not differ on the BALB/c or C57BL/6 background
- Background Sensitivity - the number of necrotic cells in the airway epithelium is increased, with a greater increase on the BALB/c background compared to the C57BL/6 background in neonates

respiratory system inflammation
- airway inflammation, with similar levels on the C57BL/6 or BALB/c backgrounds

The following phenotype relates to a compound genotype created using this strain

Genotype: Tg(Scgb1a1-Scnn1b)6608Bouc/0
involves: C3H * C57BL/6

immune system phenotype

bronchitis
- bronchoalveolar lavage (BAL) fluid and lung homogenates of adult, but not neonatal, transgenic mice contain significantly higher levels of macrophage inflammatory protein 2 (MIP-2) and KC than do those of nontransgenic littermates
- histopathologic examination of the lungs reveals evidence of chronic bronchitis, the lumina of conducting airways populated with macrophages and neutrophils; however, the submucosa contain few inflammatory cells

lung inflammation
- bronchoalveolar lavage (BAL) fluid and lung homogenates of adult, but not neonatal, transgenic mice contain significantly higher levels of macrophage inflammatory protein 2 (MIP-2) and KC than do those of nontransgenic littermates
- histopathologic examination of the lungs reveals evidence of chronic bronchitis, the lumina of conducting airways populated with macrophages and neutrophils; however, the submucosa contain few inflammatory cells

mortality/aging

postnatal lethality
- although transgenic animals are born at the expected Mendelian ratios, 50% of transgenic mice of both sexes die from the first days of postnatal life through 4 weeks of age

respiratory system phenotype

abnormal mucociliary clearance
- airway mucus of transgenic mice is significantly more concentrated than that of nontransgenic littermates; electron and light microscopy reveal adhesion of mucus to airway epithelia and reduction of periciliary liquid (PCL) height in tracheae and bronchi of transgenic mice
- lung histology of all transgenic mice is normal at birth, but those that die early exhibit severe obstruction of small and large airways by mucus plaques and plugs; those euthanized after 4 weeks have less severe mucus obstruction with dilation of airspaces distal to blockages
- the rate of clearance of a fluorescent dye demonstrates slower in vitro mucus transport in the lower airways of transgenic mice than of nontransgenic littermates, and whereas intratracheally instilled Haemophilus influenzae or Pseudomonas aeruginosa were almost completely cleared within 3 days from the lungs of wild-type mice, transgenic mice retained a significant bacterial burden

abnormal respiratory mucosa goblet cell morphology
- airway epithelia of adult transgenic mice exhibit goblet cell metaplasia

abnormal respiratory system physiology
- increased airway absorption of Na⁺ is demonstrated by elevation of basal and amiloride-sensitive short-circuit currents (I_sc) across freshly excised adult and neonatal tracheal tissue of transgenic mice over those of nontransgenic littermates; in contrast, both forskolin and UTP fail to increase chloride channel activation in amiloride pretreated transgenic tracheae above wild-type levels

bronchitis
- bronchoalveolar lavage (BAL) fluid and lung homogenates of adult, but not neonatal, transgenic mice contain significantly higher levels of macrophage inflammatory protein 2 (MIP-2) and KC than do those of nontransgenic littermates
- histopathologic examination of the lungs reveals evidence of chronic bronchitis, the lumina of conducting airways populated with macrophages and neutrophils; however, the submucosa contain few inflammatory cells

lung inflammation
- bronchoalveolar lavage (BAL) fluid and lung homogenates of adult, but not neonatal, transgenic mice contain significantly higher levels of macrophage inflammatory protein 2 (MIP-2) and KC than do those of nontransgenic littermates
- histopathologic examination of the lungs reveals evidence of chronic bronchitis, the lumina of conducting airways populated with macrophages and neutrophils; however, the submucosa contain few inflammatory cells

respiratory distress
- early deaths of transgenic mice result from asphyxia due to severe airway obstruction, evidenced by frequent observation of intercostal and subdiaphragmatic retractions

References

Hackett BP; Gitlin JD. 1992. Cell-specific expression of a Clara cell secretory protein-human growth hormone gene in the bronchiolar epithelium of transgenic mice. Proc Natl Acad Sci U S A 89(19):9079-83PubMed: 1409605 MGI: J:101823
Mall M; Grubb BR; Harkema JR; O'Neal WK; Boucher RC. 2004. Increased airway epithelial Na+ absorption produces cystic fibrosis-like lung disease in mice. Nat Med 10(5):487-93PubMed: 15077107 MGI: J:91139
Ostrowski LE; Hutchins JR; Zakel K; O'Neal WK. 2003. Targeting expression of a transgene to the airway surface epithelium using a ciliated cell-specific promoter. Mol Ther 8(4):637-45PubMed: 14529837 MGI: J:101822

Additional - Tg(Scgb1a1-Scnn1b)6608Bouc related

Technical Support

CONTACT TECHNICAL SUPPORT

Genotyping Protocols
- Standard PCR:Tg(Scgb1a1-Scnn1b)
- Sanger sequencing:Tlr4 SEQ
- Genotyping resources and troubleshooting
Breeding Considerations

When maintaining a live colony, hemizygous mice are bred to B6C3FeF1/J (Stock No. 001022; 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.
- Additional Breeding and Husbandry Support
Citation
When using the Scnn1b-Tg mouse strain in a publication, please cite the originating article(s) and include JAX stock #006176 in your Materials and Methods section.

Animal Health Reports

Facility Barrier Level Descriptions

Production of mice from cryopreserved embryos or sperm occurs in a maximum barrier room, G200

Pricing & Availability

Cryo Recovery

Domestic
International

Live Mouse

Age

Genotype

Price

weeks

Cryorecovery - Pricing

Service/Product	Description	Price
	Hemizygous or Non carrier for Tg(Scgb1a1-Scnn1b)6608Bouc

Payment Terms and Conditions

Terms are granted by individual review and stated on the customer invoice(s) and account statement. These transactions are payable in U.S. currency within the granted terms. Payment for services, products, shipping containers, and shipping costs that are rendered are expected within the payment terms indicated on the invoice or stated by contract. Invoices and account balances in arrears of stated terms may result in The Jackson Laboratory pursuing collection activities including but not limited to outside agencies and court filings.

The Jackson Laboratory's Genotype Promise

The Jackson Laboratory has rigorous genetic quality control and mutant gene genotyping programs to ensure the genetic background of JAX® Mice strains as well as the genotypes of strains with identified molecular mutations. JAX® Mice strains are only made available to researchers after meeting our standards. However, the phenotype of each strain may not be fully characterized and/or captured in the strain data sheets. Therefore, we cannot guarantee a strain's phenotype will meet all expectations. To ensure that JAX® Mice will meet the needs of individual research projects or when requesting a strain that is new to your research, we suggest ordering and performing tests on a small number of mice to determine suitability for your particular project. We do not guarantee breeding performance and therefore suggest that investigators order more than one breeding pair to avoid delays in their research.

Terms Of Use

General Terms and Conditions

Questions about Terms of Use

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Use of MICE by companies or for-profit entities requires a license prior to shipping.

Licensing Information

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Email: TechTran@jax.org

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Also Known As:Scnn1b-Tg

Donating Investigator

Genetic overview

Research Applications

Base Price

Detailed Description

Development

Expression Data

Control Suggestions

Approximate Controls

Additional Information

Selected References

Tg(Scgb1a1-Scnn1b)6608Bouc

Allele Symbol: Tg(Scgb1a1-Scnn1b)6608Bouc

Disease Terms

Characteristics of this human disease are associated with transgenes and other mutation types in the mouse.

Research Areas By Phenotype

This mouse can be used to support research in many areas including:

Mammalian Phenotype Terms by Genotype

Genotype: Tg(Scgb1a1-Scnn1b)6608Bouc/0B6.Cg-Tg(Scgb1a1-Scnn1b)6608Bouc

cellular phenotype

immune system phenotype

mortality/aging

respiratory system phenotype

Genotype: Tg(Scgb1a1-Scnn1b)6608Bouc/0C.Cg-Tg(Scgb1a1-Scnn1b)6608Bouc

cellular phenotype

immune system phenotype

mortality/aging

respiratory system phenotype

Genotype: Tg(Scgb1a1-Scnn1b)6608Bouc/0involves: C3H * C57BL/6

immune system phenotype

mortality/aging

respiratory system phenotype

References

Additional - Tg(Scgb1a1-Scnn1b)6608Bouc related

Genotyping Protocols

Breeding Considerations

Citation

Animal Health Reports

Production of mice from cryopreserved embryos or sperm occurs in a maximum barrier room, G200

Live Mouse

Cryorecovery - Pricing

Payment Terms and Conditions

The Jackson Laboratory's Genotype Promise

Terms Of Use

Additional Use Restrictions Apply

Licensing Information

JAX® Mice, Products & Services Conditions of Use

No Warranty

Credit for PRODUCTS or SERVICES

Animal Care and Use for SERVICES

No Liability

Genotype: Tg(Scgb1a1-Scnn1b)6608Bouc/0
B6.Cg-Tg(Scgb1a1-Scnn1b)6608Bouc

Genotype: Tg(Scgb1a1-Scnn1b)6608Bouc/0
C.Cg-Tg(Scgb1a1-Scnn1b)6608Bouc

Genotype: Tg(Scgb1a1-Scnn1b)6608Bouc/0
involves: C3H * C57BL/6