Description

The genotypes of the animals provided may not reflect those discussed in the strain description or the mating scheme utilized by The Jackson Laboratory prior to cryopreservation. Please inquire for possible genotypes for this specific strain.

Strain Information

Type Congenic; Mutant Strain; Targeted Mutation; Additional information on Genetically Engineered and Mutant Mice. Visit our online Nomenclature tutorial. Additional information on Congenic nomenclature. Species laboratory mouse Background Strain C57BL/6 Donor Strain 129S6 via EK.CC1.2 ES cell line Generation N5F14+N1p (01-FEB-04)   Donating Investigator Kirk Thomas,   Univ of Utah

Description
The Cftr^tm1Kth targeted mutation corresponds to the delta 508 mutation in humans. Homozygous mutant mice show an increased mortality within the first month after birth, with ~60% mortality by post-weaning. Those that survive are fertile, but females are poor breeders. Mutant mice are also reduced in size compared to normal wildtype mice. Those that do not survive to adulthood show bowel obstructions, bowel strictures and peritonitis. Lungs, pancreas, gall bladder, male reproductive tract, lacrimal gland, and submandibular glands from homozygous mice appear normal regardless of the survival of the animal. Homozygous mice also show a tissue-specific loss of CFTR transcripts in the intestine.

Development
The Cftr^tm1Kth targeted mutation was made in the laboratory of Dr. Kirk R. Thomas at the University of Utah. The mutated allele contains a 3-bp (CTT) deletion between bases 1656 and 1660 resulting in the loss of a phenylalanine residue in exon 10 at a position which corresponds to human position 508. The 129S6/SvEv-derived CC1.2 ES cell line was used.

Control Information

	Control
	Wild-type from the colony
	000664 C57BL/6J
Considerations for Choosing Controls

Related Strains

Strains carrying other alleles of Cftr

002196	B6.129P2-Cftrtm1Unc/J
002364	STOCK Cftrtm1Unc-Tg(FABPCFTR)1Jaw/J

View Strains carrying other alleles of Cftr     (2 strains)

Additional Web Information

Congenic Nomenclature

Phenotype

Phenotype Information

View Related Disease (OMIM) Terms

Related Disease (OMIM) Terms

Cystic Fibrosis; CF - Models with phenotypic similarity to human disease where etiologies involve orthologs.1

1 Human genes are associated with this disease. Orthologs of those genes appear in the mouse genotype(s).

View Mammalian Phenotype Terms

Mammalian Phenotype Terms

      assigned by genotype

Cftr^tm1Kth/Cftr^tm1Kth

        B6.129S7-Cftr^tm1Kth

• respiratory system phenotype
• abnormal respiratory system physiology (MGI Ref ID J:112450)
  • abnormal nasal potential difference
• lung inflammation (MGI Ref ID J:112450)
  • increased inflammatory response to chronic Pseudomonas aeruginosa infection, identical to that in Cftr^tm1Unc homozygotes
• growth/size phenotype
• decreased body weight (MGI Ref ID J:112450)
  • reduced at 7, 14, and 21 days of age relative to wild-type mice
• digestive/alimentary phenotype
• intestinal obstruction (MGI Ref ID J:112450)
  • develop intestinal blockage when fed a normal (solid) diet
• immune system phenotype
• lung inflammation (MGI Ref ID J:112450)
  • increased inflammatory response to chronic Pseudomonas aeruginosa infection, identical to that in Cftr^tm1Unc homozygotes

The following phenotype information may relate to a genetic background differing from this JAX^® Mice strain.

Cftr^tm1Kth/Cftr^tm1Kth

        involves: 129S7/SvEvBrd * C57BL/6J

• lethality-postnatal
• postnatal lethality (MGI Ref ID J:29074)
  • about 10% died within 7 days of birth and saw significant mortality around the time of weaning (30 days after birth), with 40% surviving postweaning for at least 8 months
• digestive/alimentary phenotype
• abnormal digestive system physiology (MGI Ref ID J:29074)
  • lacked cAMP-stimulated Cl^- secretory current in intestine, indicating defective electrolyte transport
• abnormal pancreas physiology (MGI Ref ID J:29074)
  • reduced absorption of fluid and lower cAMP-stimulated fluid secretion by pancreatic epithelia
• intestinal obstruction (MGI Ref ID J:29074)
  • mice that died prematurely showed evidence of bowel obstruction
• peritoneal inflammation (MGI Ref ID J:29074)
  • mice that died prematurely showed peritonitis
• abnormal intestine morphology (MGI Ref ID J:29074)
  • mice that died prematurely showed evidence of bowel obstruction and bowel strictures, especially in the cecum
• abnormal duodenum morphology (MGI Ref ID J:29074)
  • Brunner's glands were often dilated
• abnormal jejunum morphology (MGI Ref ID J:29074)
  • some mice exhibited large casts of mucus material in the jejunum, however lung, pancreas, gall bladder, male reproductive tract, lacrimal gland, and submandibular glands appeared normal
• growth/size phenotype
• decreased body size (MGI Ref ID J:29074)
  • reduced size noticeable as early as 10 days after birth
• decreased body weight (MGI Ref ID J:29074)
  • by weaning, weight was only 50-60% that of controls and although homozygous mutant mice continued to grow, they never reached the size of controls
• homeostasis/metabolism phenotype
• abnormal fluid regulation (MGI Ref ID J:29074)
  • defective fluid transport in nasal, intestinal, and pancreatic duct epithelia
• abnormal ion homeostasis (MGI Ref ID J:29074)
  • defective electrolyte transport in nasal, intestinal, and pancreatic duct epithelia
• immune system phenotype
• peritoneal inflammation (MGI Ref ID J:29074)
  • mice that died prematurely showed peritonitis
• endocrine/exocrine gland phenotype
• abnormal pancreas physiology (MGI Ref ID J:29074)
  • reduced absorption of fluid and lower cAMP-stimulated fluid secretion by pancreatic epithelia

View Research Applications

Research Applications

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

Immunology and Inflammation Research
Cystic Fibrosis

Cftr^tm1Kth related

Immunology and Inflammation Research
Inflammation (Inflammatory bowel disease)

Metabolism Research

Mouse/Human Gene Homologs
cystic fibrosis

Genes & Alleles

Gene & Allele Information

Allele Symbol		Cftrtm1Kth
Allele Name		targeted mutation 1, Kirk R Thomas
Allele Type		Targeted (knock-in)
Common Name(s)		CFTRdeltaF508; deltaF; deltaF508 Cftr;
Mutation Made By		Kirk Thomas,   Univ of Utah
Strain of Origin		129S7/SvEvBrd
ES Cell Line Name		CC1.2
ES Cell Line Strain		129S7/SvEvBrd
Gene Symbol and Name		Cftr, cystic fibrosis transmembrane conductance regulator homolog
Chromosome		6
Gene Common Name(s)		ABC35; ABCC7; AW495489; CF; CFTR/MRP; MRP7; RGD1561193; TNR-CFTR; dJ760C5.1; expressed sequence AW495489;
General Note		This (J:29074) and other (J:27734, J:28979) targeted mutations reproduce the common human mutation, eliminating the same phenylalanine from the protein sequence. In at least one of these models, the mutant is temperature sensitive, and can be expressed on the apical membrane when cultured at low temperatures, which is also true of the human mutant lacking the same phenylalanine residue (J:35364).
Molecular Note		The allele contains a 3 bp deletion in exon 10 of nucleotides between 1656 to 1660, resulting in the loss of a codon corresponding to a phenylalanine. A neomycin selection cassette was also inserted in intron 10 in reverse transcriptional orientation to the gene. [MGI Ref ID J:29074]

Genotyping

Genotyping Information

Genotyping Protocols

Cftr^tm1Kth, STD PCR, vers. 1

Helpful Links

Optimizing PCR Protocols

References

References

Selected Reference(s)

Zeiher BG; Eichwald E; Zabner J; Smith JJ; Puga AP; McCray PB Jr; Capecchi MR; Welsh MJ; Thomas KR. 1995. A mouse model for the delta F508 allele of cystic fibrosis. J Clin Invest 96(4):2051-64. [PubMed: 7560099]  [MGI Ref ID J:29074]

Additional References

Zdebik AA; Cuffe JE; Bertog M; Korbmacher C; Jentsch TJ. 2004. Additional disruption of the ClC-2 Cl(-) channel does not exacerbate the cystic fibrosis phenotype of cystic fibrosis transmembrane conductance regulator mouse models. J Biol Chem 279(21):22276-83. [PubMed: 15007059]  [MGI Ref ID J:89831]

Cftr^tm1Kth related

Clayburgh DR; Barrett TA; Tang Y; Meddings JB; Van Eldik LJ; Watterson DM; Clarke LL; Mrsny RJ; Turner JR. 2005. Epithelial myosin light chain kinase-dependent barrier dysfunction mediates T cell activation-induced diarrhea in vivo. J Clin Invest 115(10):2702-15. [PubMed: 16184195]  [MGI Ref ID J:101529]

Coleman FT; Mueschenborn S; Meluleni G; Ray C; Carey VJ; Vargas SO; Cannon CL; Ausubel FM; Pier GB. 2003. Hypersusceptibility of cystic fibrosis mice to chronic Pseudomonas aeruginosa oropharyngeal colonization and lung infection. Proc Natl Acad Sci U S A 100(4):1949-54. [PubMed: 12578988]  [MGI Ref ID J:107417]

Colledge WH; Abella BS; Southern KW; Ratcliff R; Jiang C; Cheng SH; MacVinish LJ; Anderson JR; Cuthbert AW; Evans MJ. 1995. Generation and characterization of a delta F508 cystic fibrosis mouse model. Nat Genet 10(4):445-52. [PubMed: 7545494]  [MGI Ref ID J:27734]

Falany JL; Greer H; Kovacs T; Sorscher EJ; Falany CN. 2002. Elevation of hepatic sulphotransferase activities in mice with resistance to cystic fibrosis. Biochem J 364(Pt 1):115-20. [PubMed: 11988083]  [MGI Ref ID J:113524]

Fiorotto R; Spirli C; Fabris L; Cadamuro M; Okolicsanyi L; Strazzabosco M. 2007. Ursodeoxycholic acid stimulates cholangiocyte fluid secretion in mice via CFTR-dependent ATP secretion. Gastroenterology 133(5):1603-13. [PubMed: 17983806]  [MGI Ref ID J:130257]

French PJ; van Doorninck JH; Peters RH; Verbeek E; Ameen NA; Marino CR; de Jonge HR; Bijman J; Scholte BJ. 1996. A delta F508 mutation in mouse cystic fibrosis transmembrane conductance regulator results in a temperature-sensitive processing defect in vivo. J Clin Invest 98(6):1304-12. [PubMed: 8823295]  [MGI Ref ID J:35364]

Guilbault C; Saeed Z; Downey GP; Radzioch D. 2007. Cystic fibrosis mouse models. Am J Respir Cell Mol Biol 36(1):1-7. [PubMed: 16888286]  [MGI Ref ID J:130524]

Hirokawa M; Takeuchi T; Chu S; Akiba Y; Wu V; Guth PH; Engel E; Montrose MH; Kaunitz JD. 2004. Cystic fibrosis gene mutation reduces epithelial cell acidification and injury in acid-perfused mouse duodenum. Gastroenterology 127(4):1162-73. [PubMed: 15480994]  [MGI Ref ID J:93426]

Kelley TJ; Drumm ML. 1998. Inducible nitric oxide synthase expression is reduced in cystic fibrosis murine and human airway epithelial cells. J Clin Invest 102(6):1200-7. [PubMed: 9739054]  [MGI Ref ID J:115209]

Kibble JD; Neal AM; Colledge WH; Green R; Taylor CJ. 2000. Evidence for cystic fibrosis transmembrane conductance regulator-dependent sodium reabsorption in kidney, using Cftr(tm2cam) mice. J Physiol 526 Pt 1:27-34. [PubMed: 10878096]  [MGI Ref ID J:134183]

Liu X; Yan Z; Luo M; Engelhardt JF. 2006. Species-specific differences in mouse and human airway epithelial biology of recombinant adeno-associated virus transduction. Am J Respir Cell Mol Biol 34(1):56-64. [PubMed: 16195538]  [MGI Ref ID J:120193]

Lu M; Leng Q; Egan ME; Caplan MJ; Boulpaep EL; Giebisch GH; Hebert SC. 2006. CFTR is required for PKA-regulated ATP sensitivity of Kir1.1 potassium channels in mouse kidney. J Clin Invest 116(3):797-807. [PubMed: 16470247]  [MGI Ref ID J:106483]

Okiyoneda T; Niibori A; Harada K; Kohno T; Michalak M; Duszyk M; Wada I; Ikawa M; Shuto T; Suico MA; Kai H. 2008. Role of calnexin in the ER quality control and productive folding of CFTR; differential effect of calnexin knockout on wild-type and DeltaF508 CFTR. Biochim Biophys Acta 1783(9):1585-94. [PubMed: 18457676]  [MGI Ref ID J:136971]

Ostedgaard LS; Rogers CS; Dong Q; Randak CO; Vermeer DW; Rokhlina T; Karp PH; Welsh MJ. 2007. Processing and function of CFTR-DeltaF508 are species-dependent. Proc Natl Acad Sci U S A 104(39):15370-5. [PubMed: 17873061]  [MGI Ref ID J:125319]

Reynaert I; Van Der Schueren B; Degeest G; Manin M; Cuppens H; Scholte B; Cassiman JJ. 2000. Morphological changes in the vas deferens and expression of the cystic fibrosis transmembrane conductance regulator (CFTR) in control, deltaF508 and knock-out CFTR mice during postnatal life. Mol Reprod Dev 55(2):125-35. [PubMed: 10618651]  [MGI Ref ID J:119599]

Schroeder TH; Reiniger N; Meluleni G; Grout M; Coleman FT; Pier GB. 2001. Transgenic cystic fibrosis mice exhibit reduced early clearance of Pseudomonas aeruginosa from the respiratory tract. J Immunol 166(12):7410-8. [PubMed: 11390493]  [MGI Ref ID J:128660]

Sidani SM; Kirchhoff P; Socrates T; Stelter L; Ferreira E; Caputo C; Roberts KE; Bell RL; Egan ME; Geibel JP. 2007. DeltaF508 mutation results in impaired gastric acid secretion. J Biol Chem 282(9):6068-74. [PubMed: 17178714]  [MGI Ref ID J:120932]

Steagall WK; Drumm ML. 1999. Stimulation of cystic fibrosis transmembrane conductance regulator-dependent short-circuit currents across DeltaF508 murine intestines. Gastroenterology 116(6):1379-88. [PubMed: 10348821]  [MGI Ref ID J:55783]

Zdebik AA; Cuffe JE; Bertog M; Korbmacher C; Jentsch TJ. 2004. Additional disruption of the ClC-2 Cl(-) channel does not exacerbate the cystic fibrosis phenotype of cystic fibrosis transmembrane conductance regulator mouse models. J Biol Chem 279(21):22276-83. [PubMed: 15007059]  [MGI Ref ID J:89831]

van Doorninck JH; French PJ; Verbeek E; Peters RH; Morreau H; Bijman J; Scholte BJ. 1995. A mouse model for the cystic fibrosis delta F508 mutation. EMBO J 14(18):4403-11. [PubMed: 7556083]  [MGI Ref ID J:28979]

van Heeckeren AM; Schluchter MD; Drumm ML; Davis PB. 2004. Role of Cftr genotype in the response to chronic Pseudomonas aeruginosa lung infection in mice. Am J Physiol Lung Cell Mol Physiol 287(5):L944-52. [PubMed: 15246977]  [MGI Ref ID J:112450]

Health & husbandry

The genotypes of the animals provided may not reflect those discussed in the strain description or the mating scheme utilized by The Jackson Laboratory prior to cryopreservation. Please inquire for possible genotypes for this specific strain.

Health & Colony Maintenance Information

Colony Maintenance

Breeding & Husbandry	This strain is currently being maintained by mating heterozygous siblings; this is the most effective breeding strategy. Homozygous males will breed while homozygous females are very poor breeders. Expected coat color from breeding:Black
Diet Information	LabDiet® 5K52/5K67

Purchasing information

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

Pricing

Supply Details

Standard Supply

Cryopreserved. Ready for recovery. Please refer to pricing and supply notes for further information.

Supply Notes

Cryorecovery - Standard. At least two mice that carry the mutation (if it is a mutant strain) will be provided. The total number of animals provided, their gender and genotype will vary. Please inquire if larger numbers of animals with specific genotypes and genders are needed. IMPORTANT NOTE: The genotypes of the animals provided may not reflect the mating scheme utilized by The Jackson Laboratory prior to cryopreservation, or that discussed in the strain description. Please inquire for possible genotypes for this specific strain. Animals typically ship within 13 to 16 weeks from your order. If a second cryorecovery is needed in order to provide the minimum number of animals, animals will typically ship within 25 weeks. Cryorecovery to establish a Dedicated Supply for greater quantities of mice. One to two pairs will be recovered to establish a Dedicated Supply of mice. Price by quotation. For more information on Dedicated Supply, please contact JAX® Services, Tel: 1-800-422-6423 or 1-207-288-5845. This strain is included in the Induced Mutant Resource Colony collection. Genomic DNA is available for this strain from the Mouse DNA Resource.

Control Information

	Control
	Wild-type from the colony
	000664 C57BL/6J
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

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.

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Ordering and Purchasing Information

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Tel: 800.422.6423 or 207.288.5845
Fax: 207.288.6150
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Terms of Use

Terms of Use

General Terms and Conditions

Contact information

General inquiries

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phone:	207-288-6470
fax:	207-288-6655

JAX^® Mice & Services Conditions of Use

“Each recipient institution, including its employees and other researchers under its control (RECIPIENT), of mice or services using mice from The Jackson Laboratory (TJL) agrees that such mice, descendants of those mice derived by inbreeding or crossbreeding, including unmodified derivatives of those mice or their descendants (“MICE”) shall not be: (i) used for any purpose other than the internal research of the RECIPIENT, (ii) sold or otherwise provided to any third party for any use, or (iii) provided to any agent or other third party to provide breeding or other services with respect to MICE. Acceptance of MICE from TJL shall be deemed agreement by RECIPIENT to these conditions, and departure from these conditions requires The Jackson Laboratory’s prior written authorization.”

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Acceptance of delivery of MICE, products or services shall be deemed agreement to these terms and conditions. No purchase order or other document transmitted by purchaser or recipient that may modify the terms and conditions hereof, shall be in any way binding on The Jackson Laboratory, and instead the terms and conditions set forth herein, including any special terms and conditions set forth separately, shall govern the sale of MICE, products services by The Jackson Laboratory.