Overview

Also Known As: ΔF

These Cftr knock-out mice exhibit neonatal lethality with abnormal bowel development. They may be useful in applications related to the study of cystic fibrosis.

Donating Investigator

Dr. Kirk R. Thomas, Univ of Utah

Genetic overview

Genetic Background	Generation

Cftr^tm1Kth

Allele Type	Gene Symbol	Gene Name
Targeted (Hypomorph)	Cftr	cystic fibrosis transmembrane conductance regulator

View Genetics

Research Applications

Immunology, Inflammation and Autoimmunity Research
Metabolism Research
Mouse/Human Gene Homologs

View All Research Applications

Base Price

Starting at:

$2,854.50 Domestic price Cryo Recovery

View Price List

Details

Detailed 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 Suggestions

Wild-type from the colony
000664 C57BL/6J

Additional Information

Considerations for Choosing Controls

Selected References

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):2051-64PubMed: 7560099 MGI: J:29074

View All References

Genetics

Cftr^tm1Kth

Allele Symbol: Cftr^tm1Kth

Allele Name	targeted mutation 1, Kirk R Thomas
Allele Type	Targeted (Hypomorph)
Allele Synonym(s)	targeted mutation 1, Kirk R Thomas; Cftr^tm1Kth
Gene Symbol and Name	Cftr, cystic fibrosis transmembrane conductance regulator
Gene Synonym(s)	CFTR/MRP; dJ760C5.1; ABC35; AW495489; MRP7; TNR-CFTR; ABCC7; CF; expressed sequence AW495489; RGD1561193; Abcc7
Promoter	Cftr, cystic fibrosis transmembrane conductance regulator, mouse, laboratory
Strain of Origin	129S7/SvEvBrd
Chromosome	6
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 11 resulting in the loss of phenylalanine codon 508 (p.F508del). This deletion mimics the deltaF508 mutation found in human cystic fibrosis patients. A neomycin selection cassette was also inserted in intron 11 in reverse transcriptional orientation to the gene. In salivary glands transcription levels from the allele are comparable to wild-type, but no protein was detected. Protein was detected in testes but it was mislocalized. Transcription levels in intestine were greatly reduced.
Mutations Made By	Dr. Kirk Thomas, Univ of Utah

Disease/Phenotype

Disease Terms

Model with phenotypic similarity to human disease where etiologies involve orthologs. Human genes are associated with this disease. Orthologs of those genes appear in the mouse genotype(s).

cystic fibrosis

Research Areas By Genotype

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

Immunology, Inflammation and Autoimmunity Research
- Cystic Fibrosis

Genotype: Cftr^tm1Kth related

Metabolism Research
Mouse/Human Gene Homologs
- cystic fibrosis
Immunology, Inflammation and Autoimmunity Research
- Inflammation
  - Inflammatory bowel disease

Mammalian Phenotype Terms by Genotype

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

Genotype: Cftr^tm1Kth/Cftr^tm1Kth
involves: 129S7/SvEvBrd * C57BL/6J

digestive/alimentary phenotype

abnormal digestive system physiology
- lacked cAMP-stimulated Cl^- secretory current in intestine, indicating defective electrolyte transport

abnormal intestine morphology
- mice that died prematurely showed evidence of bowel obstruction and bowel strictures, especially in the cecum

abnormal jejunum morphology
- 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

dilated Brunner's glands
- Brunner's glands were often dilated

intestinal obstruction
- mice that died prematurely showed evidence of bowel obstruction

peritoneal inflammation
- mice that died prematurely showed peritonitis

homeostasis/metabolism phenotype

abnormal fluid regulation
- defective fluid transport in nasal, intestinal, and pancreatic duct epithelia

abnormal ion homeostasis
- defective electrolyte transport in nasal, intestinal, and pancreatic duct epithelia

immune system phenotype

peritoneal inflammation
- mice that died prematurely showed peritonitis

mortality/aging

postnatal lethality, incomplete penetrance
- 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

endocrine/exocrine gland phenotype

abnormal pancreas physiology
- reduced absorption of fluid and lower cAMP-stimulated fluid secretion by pancreatic epithelia

dilated Brunner's glands
- Brunner's glands were often dilated

growth/size/body region phenotype

decreased body size
- reduced size noticeable as early as 10 days after birth

decreased body weight
- 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

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

Genotype: Cftr^tm1Kth/Cftr^tm1Kth
B6.129S7-Cftr

digestive/alimentary phenotype

intestinal obstruction
- develop intestinal blockage when fed a normal (solid) diet

mammalian phenotype

homeostasis/metabolism phenotype
- Normal - although mutant FSH levels are slightly increased relative to wild-type levels, circulating levels of both FSH and LH still remain within normal range at proestrus

mortality/aging

increased susceptibility to bacterial infection induced morbidity/mortality
- reduced ability to respond to lung infection elicited with Pseudomonas aeruginosa- laden agarose beads

reproductive system phenotype

abnormal sperm physiology
- Normal - however, no differences in capacitation of oviductal sperm from mutant and wild-type females are observed
- sperm transport within the mutant female reproductive system is significantly impaired: the average number of sperm found in mutant oviducts is only ~10% that of wild-type

abnormal uterine cervix morphology
- only 1 of 15 female homozygotes showed cervical mucus accumulation with no other physical signs of obstruction in the uterus

absent estrous cycle
- unlike wild-type females, 22.2% of 14-16-wk-old mutant females never enter estrus but are constantly in diestrus

decreased corpora lutea number
- female homozygotes show an average of 1.5 +/- 2.0 corpora lutea per ovary vs 9.3 +/- 1.4 in wild-type females, even though other follicle stages are present

decreased litter size
- female homozygotes show a significant decrease in average number of pups per litter relative to wild-type females (3.81 +/- 1.43 vs 6.56 +/- 2.36, respectively)

decreased ovary weight
- at 6-8 and 14-16 weeks of age, the average weight of mutant ovaries is reduced by 50% and 36%, respectively, relative to that of wild-type ovaries
- Normal - however, mutant ovarian weight is restored to wild-type values after superovulation

decreased ovulation rate
- female homozygotes display reduced oocyte ovulation rates relative to wild-type females
- Normal - however, normal ovulation rates are observed after induction of superovulation with exogenous hormone (PMSG + hCG) injections

decreased uterus weight
- at 6-8 and 14-16 weeks of age, the average weight of mutant uteri is reduced by 56% and 36%, respectively, relative to that of wild-type uteri
- Normal - however, mutant uterus weight is restored to wild-type values after superovulation

delayed sexual maturation
- female homozygotes display a delayed onset of puberty relative to wild-type controls

impaired fertilization
- at 48 hrs after hCG treatment, 98.4% of mutant oocytes remain unfertilized, whereas the majority of embryos from superovulated wild-type females are found at the 2- to 4-cell stages
- however, no significant differences in in vitro fertilization rates are observed, suggesting that decreased in vivo fertilization is more likely due to inadequate fluid control in the reproductive tract, resulting in decreased sperm number in the oviduct

prolonged estrous cycle
- at 14-16 weeks of age, female homozygotes that display at least one estrous cycle show half as many cycles as wild-type females, resulting in a 2-fold increase in average cycle length

reduced female fertility
- 35.7% of female homozygotes are unable to give birth over a 5-month mating period
- female homozygotes exhibit reduced fertility with significantly fewer numbers of litters and smaller litter sizes relative to wild-type females
- following induction of superovulation, only 1 of 10 mutant females that displayed vaginal plugs gave birth, but that female did give birth to 20 pups

small ovary
- at 7 weeks of age, female homozygotes display smaller ovaries than wild-type females

small uterus
- at 7 weeks of age, female homozygotes display smaller uteri than wild-type females

thin uterus
- mutant uteri are thinner than wild-type

endocrine/exocrine gland phenotype

decreased corpora lutea number
- female homozygotes show an average of 1.5 +/- 2.0 corpora lutea per ovary vs 9.3 +/- 1.4 in wild-type females, even though other follicle stages are present

decreased ovary weight
- at 6-8 and 14-16 weeks of age, the average weight of mutant ovaries is reduced by 50% and 36%, respectively, relative to that of wild-type ovaries
- Normal - however, mutant ovarian weight is restored to wild-type values after superovulation

small ovary
- at 7 weeks of age, female homozygotes display smaller ovaries than wild-type females

respiratory system phenotype

decreased respiratory epithelial chloride transmembrane transport
- after treatment with a chloride-depleted solution with amiloride and forskolin, the nasal potential difference (PD) was significantly different between control mice and homozygous mice

lung inflammation
- increased inflammatory response to chronic Pseudomonas aeruginosa infection, identical to that in Cftr^tm1Unc homozygotes

growth/size/body region phenotype

postnatal growth retardation
- at 6-8 and 14-16 weeks of age, total body weight is reduced by only 15% and 12%, respectively, thus not explaining the larger differences noted in average weight of reproductive organs (~50% and 36%, respectively)
- weighed significantly less (P 0.05) than homozygote wild-type controls at 7, 14, and 21 days of age

immune system phenotype

increased susceptibility to bacterial infection induced morbidity/mortality
- reduced ability to respond to lung infection elicited with Pseudomonas aeruginosa- laden agarose beads

lung inflammation
- increased inflammatory response to chronic Pseudomonas aeruginosa infection, identical to that in Cftr^tm1Unc homozygotes

References

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):2051-64PubMed: 7560099 MGI: 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):22276-83PubMed: 15007059 MGI: J:89831

Additional - Cftr^tm1Kth related

Technical Support

Contact Technical Support

Genotyping Protocols
- Standard PCR: Cftr^tm1Kth
- Genotyping resources and troubleshooting
Breeding Considerations

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
- Additional Breeding and Husbandry Support
Citation
When using the ΔF mouse strain in a publication, please cite the originating article(s) and include JAX stock #002515 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	Genotype	Price
	Heterozygous or Wild-type for Cftr<tm1Kth>

We will fulfill your order by providing at least two carriers for each strain ordered. The total number, sex, and genotypes provided will vary, although typically 8 or more animals are provided. Please check genotypes which will be recovered. While the genotypes of all animals produced will be communicated to you prior to scheduling shipment, the genotypes of animals provided may not reflect the mating scheme and genotypes described in the strain description. Animals are typically ready to ship in 11-14 weeks. If a second recovery is required to produce the minimum number of animals, then delivery time would increase to approximately 25 weeks. If we fail to produce animals of the correct genotype, you will not be charged. We cannot guarantee the reproductive success of mice shipped to your facility. If the mice are lost after the first three days (post-arrival) or do not produce progeny at your facility, a new order and fee will be necessary.

Cryorecovery to establish a Dedicated Supply for greater quantities of mice. Mice recovered can be used to establish a dedicated colony to contractually supply you mice according to your requirements. Price by quotation.

Related Products and Services

Frozen Mouse Embryo

$2,595.00 per straw or vial

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.

Terms Of Use

Terms of Use

General Terms and Conditions

Questions about Terms of Use

Licensing Information

Phone: 207-288-6470

Email: TechTran@jax.org

JAX® Mice, Products & Services Conditions of Use

"MICE" means mouse strains, their progeny derived by inbreeding or crossbreeding, unmodified derivatives from mouse strains or their progeny supplied by The Jackson Laboratory ("JACKSON"). "PRODUCT(S)" means biological materials supplied by JACKSON, and their derivatives. "SERVICES" means projects conducted by JACKSON for other parties that may include but are not limited to the use of MICE or PRODUCTS. "RECIPIENT" means each recipient of MICE, PRODUCTS, or SERVICES provided by JACKSON including each institution, its employees and other researchers under its control. MICE or PRODUCTS shall not be: (i) used for any purpose other than internal research, (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. Acceptance of MICE, PRODUCTS or SERVICES from JACKSON shall be deemed as agreement by RECIPIENT to these conditions, and departure from these conditions requires JACKSON’s prior written authorization.

No Warranty

MICE, PRODUCTS AND SERVICES ARE PROVIDED "AS IS". JACKSON EXTENDS NO WARRANTIES OF ANY KIND, EITHER EXPRESS, IMPLIED, OR STATUTORY, WITH RESPECT TO MICE, PRODUCTS OR SERVICES, INCLUDING ANY IMPLIED WARRANTY OF MERCHANTABILITY OR FITNESS FOR A PARTICULAR PURPOSE, OR ANY WARRANTY OF NON-INFRINGEMENT OF ANY PATENT, TRADEMARK, OR OTHER INTELLECTUAL PROPERTY RIGHTS.

Credit for PRODUCTS or SERVICES

In case of dissatisfaction for a valid reason and claimed in writing by a purchaser within ninety (90) days of receipt of, PRODUCTS or SERVICES, JACKSON will, at its option, provide credit or replacement for the PRODUCT received or the SERVICES provided; JACKSON makes no other representations and this shall be the exclusive remedy of the purchaser. Please note specific policy for live mice.

Animal Care and Use for SERVICES

Consistent with the requirement for a written understanding regarding animal care and use, the JACKSON Animal Care and Use Committee will review the animal care and use protocol(s) associated with any SERVICES to be performed at JACKSON, and JACKSON shall have ultimate responsibility and authority for the care of animals while on site or in JACKSON custody.

No Liability

In no event shall JACKSON, its trustees, directors, officers, employees, and affiliates be liable for any causes of action or damages, including any direct, indirect, special, or consequential damages, arising out of the provision of MICE, PRODUCTS, or SERVICES, including economic damage or injury to property and lost profits, and including any damage arising from acts or negligence on the part of JACKSON, its agents or employees. Unless prohibited by law, in purchasing or receiving MICE, PRODUCTS, or SERVICES from JACKSON, purchaser or recipient, or any party claiming by or through them, expressly releases and discharges JACKSON from all such causes of action or damages, and further agrees to defend and indemnify JACKSON from any costs or damages arising out of any third party claims.

MICE, PRODUCTS or SERVICES are to be used in a safe manner and in accordance with all applicable governmental rules and regulations.

The foregoing represents the General Terms and Conditions applicable to JACKSON’s MICE, PRODUCTS or SERVICES. In addition, special terms and conditions of sale of certain MICE, PRODUCTS, or SERVICES may be set forth separately in JACKSON web pages, catalogs, price lists, contracts, and/or other documents, and these special terms and conditions shall also govern the sale of these MICE, PRODUCTS and SERVICES by JACKSON, and by its licensees and distributors.

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 JACKSON, 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 or SERVICES by JACKSON.

Also Known As: ΔF

Donating Investigator

Genetic overview

Research Applications

Base Price

Detailed Description

Development

Control Suggestions

Additional Information

Selected References

Cftrtm1Kth

Allele Symbol: Cftrtm1Kth

Disease Terms

Model with phenotypic similarity to human disease where etiologies involve orthologs. Human genes are associated with this disease. Orthologs of those genes appear in the mouse genotype(s).

Research Areas By Genotype

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

Genotype: Cftrtm1Kth related

Mammalian Phenotype Terms by Genotype

Genotype: Cftrtm1Kth/Cftrtm1Kthinvolves: 129S7/SvEvBrd * C57BL/6J

digestive/alimentary phenotype

homeostasis/metabolism phenotype

immune system phenotype

mortality/aging

endocrine/exocrine gland phenotype

growth/size/body region phenotype

Genotype: Cftrtm1Kth/Cftrtm1KthB6.129S7-Cftr

digestive/alimentary phenotype

mammalian phenotype

mortality/aging

reproductive system phenotype

endocrine/exocrine gland phenotype

respiratory system phenotype

growth/size/body region phenotype

immune system phenotype

References

Additional References

Additional - Cftrtm1Kth 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

Related Products and Services

Payment Terms and Conditions

The Jackson Laboratory's Genotype Promise

Terms of Use

Licensing Information

JAX® Mice, Products & Services Conditions of Use

No Warranty

Credit for PRODUCTS or SERVICES

Animal Care and Use for SERVICES

No Liability

Cftr^tm1Kth

Allele Symbol: Cftr^tm1Kth

Genotype: Cftr^tm1Kth related

Genotype: Cftr^tm1Kth/Cftr^tm1Kth
involves: 129S7/SvEvBrd * C57BL/6J

Genotype: Cftr^tm1Kth/Cftr^tm1Kth
B6.129S7-Cftr

Additional - Cftr^tm1Kth related