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- Description
- Phenotype
- Genes & alleles
- Genotyping
- Health & husbandry
- References
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Description
Strain Information
Type Mutant Stock; Transgenic; Additional information on Genetically Engineered Mutant Mice. Mating System See Colony Maintenance Species laboratory mouse Generation N?+N2pN1 Donating Investigator Wanda O'Neal, Univ. of North Carolina at Chapel Hill 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. Approximately 40-60% of hemizygous mice die between birth and 4 weeks of age due to airway obstruction asphyxia. 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), and C57BL6-congenic (Stock No. 006438).Importation of this model was supported by The Boomer Esiason Foundation.
Development
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.
Control Information
| Control | ||
|---|---|---|
| Noncarrier | ||
| 100010 B6C3F1/J | ||
| Considerations for Choosing Controls | ||
Related Strains
Strains carrying Tg(Scgb1a1-Scnn1b)6608Bouc allele
006438 B6.Cg-Tg(Scgb1a1-Scnn1b)6608Bouc/J 006176 B6C3Fe-Tg(Scgb1a1-Scnn1b)6608Bouc/J View Strains carrying Tg(Scgb1a1-Scnn1b)6608Bouc (2 strains)
006232 B6.Cg-Tg(Scgb1a1-rtTA)1Jaw/J 006242 C.Cg-Tg(Scgb1a1-rtTA)1Jaw/J 006222 FVB.Cg-Tg(Scgb1a1-rtTA)1Jaw/J
Additional Web Information
Genetic Quality Control Annual Report
Phenotype
Phenotype Information
assigned by genotype
Tg(Scgb1a1-Scnn1b)6608Bouc/0
involves: C3H * C57BL/6
- respiratory system phenotype
- abnormal respiratory mucosa goblet cell morphology (MGI Ref ID J:91139)
- airway epithelia of adult transgenic mice exhibit goblet cell metaplasia
- abnormal respiratory system physiology (MGI Ref ID J:91139)
- increased airway absorption of Na+ is demonstrated by elevation of basal and amiloride-sensitive short-circuit currents (Isc) 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 wildtype levels
- abnormal mucociliary clearance (MGI Ref ID J:91139)
- 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
- 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
- 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 wildtype mice, transgenic mice retained a significant bacterial burden
- lung inflammation (MGI Ref ID J:91139)
- 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
- 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
- respiratory distress (MGI Ref ID J:91139)
- early deaths of transgenic mice result from asphyxia due to severe airway obstruction, evidenced by frequent observation of intercostal and subdiaphragmatic retractions
- lethality-postnatal
- postnatal lethality (MGI Ref ID J:91139)
- 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
- immune system phenotype
- lung inflammation (MGI Ref ID J:91139)
- 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
- 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
This mouse can be used to support research in many areas including:
Developmental Biology Research
Internal/Organ Defects (lung)
Perinatal Lethality
Immunology and Inflammation Research
Cystic Fibrosis
Internal/Organ Research
Lung Defects
Mouse/Human Gene Homologs
cystic fibrosis
Genes & Alleles
Gene & Allele Information
| Allele Symbol | Tg(Scgb1a1-Scnn1b)6608Bouc | ||
|---|---|---|---|
| Allele Name | transgene insertion 6608, Richard Boucher | ||
| Allele Type | Transgenic (random, expressed) | ||
| Mutation Made By | Wanda O'Neal, Univ. of North Carolina at Chapel Hill | ||
| Strain of Origin | (C3H x C57BL/6)F1 | ||
| Expressed Gene | Scnn1b, sodium channel, nonvoltage-gated 1 beta, mouse, laboratory | ||
| Promoter | Scgb1a1, secretoglobin, family 1A, member 1 (uteroglobin), rat | ||
| 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. [MGI Ref ID J:101822] [MGI Ref ID J:101823] [MGI Ref ID J:91139] | ||
Genotyping
Genotyping Information
Genotyping Protocols
Tg(Scgb1a1-Scnn1b)6608Bouc, STD PCR, vers. 1
Helpful Links
Optimizing PCR Protocols
References
References
Selected Reference(s)
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):487-93. [PubMed: 15077107] [MGI Ref ID J:91139]
Additional References
Tg(Scgb1a1-Scnn1b)6608Bouc relatedHackett 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):9079-83. [PubMed: 1409605] [MGI Ref ID J:101823]
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):637-45. [PubMed: 14529837] [MGI Ref ID J:101822]
Health & husbandry
Health & Colony Maintenance Information
Colony Maintenance
Breeding & Husbandry 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. Mating System See above
Purchasing information
Pricing, Supply Level & Notes, Controls, General Terms & Conditions
Pricing
| Pricing for USA, Canada and Mexico shipping destinations |
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*Price(s) in US dollars ($)
Weeks of Age Price* Gender Cryorecovery Fee $1900.00
Additional Supply Details
| Pricing for International shipping destinations |
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*Price(s) in US dollars ($)
Weeks of Age Price* Gender Cryorecovery Fee $2470.00
Additional Supply Details
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Supply Details
| Standard Supply | Repository-Cryopreserved. Must Be Recovered. Please refer to pricing and supply notes for further information. |
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| Supply Notes |
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Control Information
| Control | ||
|---|---|---|
| Noncarrier | ||
| 100010 B6C3F1/J | ||
| Considerations for Choosing Controls | ||
| USA, Canada and Mexico - Control Pricing Information for Genetically Engineered Mutant Strains. | ||
| International - Control Pricing Information for Genetically Engineered Mutant Strains. | ||
General Terms and Conditions
See Terms of Use
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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.Ordering and Purchasing Information
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