Description

Strain Information

Type Mutant Stock; Transgenic; Additional information on Genetically Engineered Mutant Mice. Mating System Noncarrier x Hemizygote         (Female x Male) Species laboratory mouse Generation N4 (03-DEC-07)   Donating Investigator IMR Colony,   The Jackson Laboratory

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%) survive past postnatal day 14, hemizygous mice 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), and C57BL6-congenic (Stock No. 006438).

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.

Control Information

	Control
	Noncarrier
	001022 B6C3FeF1/J a/a	(approximate)
Considerations for Choosing Controls

Related Strains

Strains carrying   Tg(Scgb1a1-Scnn1b)6608Bouc allele

006438	B6.Cg-Tg(Scgb1a1-Scnn1b)6608Bouc/J
005315	B6;C3H-Tg(Scgb1a1-Scnn1b)6608Bouc/J

View Strains carrying   Tg(Scgb1a1-Scnn1b)6608Bouc     (2 strains)

Strains carrying other alleles of Scgb1a1

006232	B6.Cg-Tg(Scgb1a1-rtTA)1Jaw/J
006242	C.Cg-Tg(Scgb1a1-rtTA)1Jaw/J
006222	FVB.Cg-Tg(Scgb1a1-rtTA)1Jaw/J

View Strains carrying other alleles of Scgb1a1     (3 strains)

Phenotype

Phenotype Information

View Related Disease (OMIM) Terms

Related Disease (OMIM) Terms

Cystic Fibrosis; CF -

View Mammalian Phenotype Terms

Mammalian Phenotype Terms

      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 (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 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

View Research Applications

Research Applications

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

Developmental Biology Research
Internal/Organ Defects (lung)

Immunology and Inflammation Research
Cystic Fibrosis

Internal/Organ Research
Lung Defects

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)

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):9079-83. [PubMed: 1409605]  [MGI Ref ID 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):487-93. [PubMed: 15077107]  [MGI Ref ID 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):637-45. [PubMed: 14529837]  [MGI Ref ID J:101822]

Health & husbandry

Health & Colony Maintenance Information

Animal Health Reports

Room Number           AX11

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	Noncarrier x Hemizygote         (Female x Male)
Diet Information	LabDiet® 5K52/5K67

Purchasing information

Pricing, Supply Level & Notes, Controls, General Terms & Conditions

Pricing

Supply Details

Standard Supply

Repository-Live. A collection of over 1000 strains maintained as live colonies. Individual colonies are sized to meet current customer demand. Delivery for orders of 10 mice or less ranges on average from one to eight weeks; mice are generally shipped between four to six weeks of age with a maximum shipping age of ~nine weeks. Colony sizes do not generally support stringent age specifications for large volumes of mice; however custom orders and larger quantities of mice are easily arranged. Estimated ship dates for all orders provided within 48 hours of order placement.

Supply Notes

Usually shipped between four and eight weeks of age. This strain is included in the Induced Mutant Resource Colony collection.

Control Information

	Control
	Noncarrier
	001022 B6C3FeF1/J a/a	(approximate)
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

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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.

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