Description

Strain Information

Type Congenic; Mutant Strain; Targeted Mutation; Additional information on Genetically Engineered Mutant Mice. Species laboratory mouse   Donating Investigator Thomas Schwarz,   Harvard University

Description
Mice that are homozygous for the targeted mutation have a complete cleft of the secondary palate and die within 12 hours of birth. Heterozygotes are viable, fertile, normal in size and do not display any gross physical or behavioral abnormalities. No gene product (mRNA or protein) is detected by Northern blot analysis of cardiac tissue or Southern blot analysis. Inwardly rectifying potassium ion currents are absent in cerebral artery myocytes and cardiac ventribular myocytes isolated from homozygote neonates. Elevated external potassium ion concentrations do not dilate isolated neonatal cerebral arteries. Homozygotes exhibit altered electrocardiogram profiles indicative of reduced heart rate and bradycardia. This mutant mouse strain may be useful in studies of potassium ion dependent vasodilation, cardiac arrythmia such as Anderson syndrome, cleft palate and developmental bone malformation.

Development
A targeting vector containing neomycin resistance and herpes simplex virus thymidine kinase genes was used to disrupt the entire open reading frame. The construct was electroporated into 129-derived R1 embryonic stem (ES) cells. Correctly targeted ES cells were injected into C57BL/6 blastocysts.

Control Information

	Control
	Wild-type from the colony
	001800 FVB/NJ
Considerations for Choosing Controls

Additional Web Information

Congenic Nomenclature

Phenotype

Phenotype Information

View Mammalian Phenotype Terms

Mammalian Phenotype Terms

      assigned by genotype

Kcnj2^tm1Swz/Kcnj2^tm1Swz

        involves: 129S1/Sv * 129X1/SvJ * FVB

• lethality-prenatal/perinatal
• neonatal lethality (MGI Ref ID J:78077)
  • all homozygous null mice died within 12 hours after birth
• cardiovascular system phenotype
• abnormal vasodilation (MGI Ref ID J:78077)
  • notably, inwardly rectifying K+ currents were absent in arterial myocytes isolated from homozygous null mice, whereas voltage-dependent K+ currents appeared unaffected relative to wild-type
  • when the the extracellular K+ concentration was increased from 6 to 15 mmol/L, cerebral arteries from homozygous null mice failed to dilate, although neonatal arteries from wild-type mice did dilate
  • cerebral arteries in mutant mice remained responsive to forskolin and to changes in Ca2+ influx, indicating that other vasodilatory mechanisms remained intact
• craniofacial phenotype
• abnormal maxilla morphology (MGI Ref ID J:78077)
  • the mutant maxilla appeared to be slightly narrow relative to wild-type; however, no defects in any of the other bones and cartilage derived from the first pharyngeal arch were observed
• abnormal palatine bone morphology (MGI Ref ID J:78077)
  • in homozygoys null mice, the small palatal shelves were present at either side, and the nasal and oral cavities appeared contiguous
• cleft palate (MGI Ref ID J:78077)
  • all homozygous null pups exhibited complete cleft of the secondary palate regardless of strain background; other facial midline structures appeared unaffected
  • the cleft was wide and prevented mutant pups from nursing, leading to dehydration
• homeostasis/metabolism phenotype
• cyanosis (MGI Ref ID J:78077)
  • most homozygous null pups became cyanotic
• respiratory system phenotype
• respiratory distress (MGI Ref ID J:78077)
  • most homozygous null pups gasped for breath
  • soon after birth, mutant pups displayed a gradual swelling of their stomach and small bowel with air
• skeleton phenotype
• abnormal maxilla morphology (MGI Ref ID J:78077)
  • the mutant maxilla appeared to be slightly narrow relative to wild-type; however, no defects in any of the other bones and cartilage derived from the first pharyngeal arch were observed
• abnormal palatine bone morphology (MGI Ref ID J:78077)
  • in homozygoys null mice, the small palatal shelves were present at either side, and the nasal and oral cavities appeared contiguous
• digestive/alimentary phenotype
• cleft palate (MGI Ref ID J:78077)
  • all homozygous null pups exhibited complete cleft of the secondary palate regardless of strain background; other facial midline structures appeared unaffected
  • the cleft was wide and prevented mutant pups from nursing, leading to dehydration

View Research Applications

Research Applications

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

Kcnj2^tm1Swz related

Cardiovascular Research
Heart Abnormalities (bradycardia)
Vascular Defects

Cell Biology Research
Channel and Transporter Defects (potassium)

Developmental Biology Research
Craniofacial and Palate Defects (cleft palate and cleft lip)

Internal/Organ Research
Heart Abnormalities (bradycardia)

Genes & Alleles

Gene & Allele Information

Allele Symbol		Kcnj2tm1Swz
Allele Name		targeted mutation 1, Thomas L Schwarz
Allele Type		Targeted (knock-out)
Common Name(s)		Kir2.1-/-;
Mutation Made By		Joshua Zaritsky,   Harvard University
Strain of Origin		(129X1/SvJ x 129S1/Sv)F1-Kitl+
ES Cell Line Name		R1
ES Cell Line Strain		(129X1/SvJ x 129S1/Sv)F1-Kitl<+>
Gene Symbol and Name		Kcnj2, potassium inwardly-rectifying channel, subfamily J, member 2
Chromosome		11
Gene Common Name(s)		HHBIRK1; HHIRK1; IRK1; K+ voltage gated channel, inward rectifier 1; KIR2.1; Kcnf1; LQT7; SQT3;
Molecular Note		The entire open reading frame of the endogenous gene was deleted by the insertion of a neomycin selection cassette. [MGI Ref ID J:78077]

Genotyping

Genotyping Information

Genotyping Protocols

Kcnj2^tm1Swz, STD PCR, vers. 1

Helpful Links

Optimizing PCR Protocols

References

References

Selected Reference(s)

Zaritsky JJ; Eckman DM; Wellman GC; Nelson MT; Schwarz TL. 2000. Targeted disruption of Kir2.1 and Kir2.2 genes reveals the essential role of the inwardly rectifying K(+) current in K(+)-mediated vasodilation. Circ Res 87(2):160-6. [PubMed: 10904001]  [MGI Ref ID J:78077]

Additional References

Kcnj2^tm1Swz related

Zaritsky JJ; Redell JB; Tempel BL; Schwarz TL. 2001. The consequences of disrupting cardiac inwardly rectifying K(+) current (I(K1)) as revealed by the targeted deletion of the murine Kir2.1 and Kir2.2 genes. J Physiol 533(Pt 3):697-710. [PubMed: 11410627]  [MGI Ref ID J:106468]

Health & husbandry

Health & Colony Maintenance Information

Colony Maintenance

Breeding & Husbandry	The resulting chimeric animals were crossed to FVB mice, and then backcrossed to the same for 10 generations. The strain is maintained as a heterozygote due to neonatal homozygous lethality.
Diet Information	LabDiet® 5K52/5K67

Purchasing information

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

Pricing

Supply Details

Standard Supply

Repository-Cryopreserved. Must Be Recovered. Please refer to pricing and supply notes for further information.

Supply Notes

Cryopreserved Embryos This strain is also available as cryopreserved embryos from our Repository. Orders for cryopreserved embryos are supplied subject to a signed agreement that must be returned to the Customer Service Department after order placement. Experienced technicians at The Jackson Laboratory have recovered frozen embryos of this strain successfully. We will provide you enough embryos to perform two embryo transfers. The Jackson Laboratory does not guarantee successful recovery at your facility. For complete information on purchasing embryos from our repository, please visit our Cryopreserved Embryos web page. Cryorecovery - Standard. The recovery process begins when a signed agreement form is returned to the Customer Service Department after order placement. Although results vary by strain, at least two males and two females (two pairs) will be provided, typically within 15 weeks of our receipt of the signed agreement form. If the first recovery attempt is unsuccessful or only one pair is recovered, a second recovery will be done, extending the delivery time to approximately 25 weeks. At least one member of each pair will be of known genotype and will carry the mutation if it is a mutant strain. Please note that pairs may not reflect the mating scheme utilized by The Jackson Laboratory prior to cryopreservation of the strain. Mating schemes are sometimes modified for successful cryopreservation. Price represents a repository maintenance fee, which includes the cost of recovery of the strain from the cryopreservation resource and the periodic replacement of the frozen embryos used for recovery. 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.

Control Information

	Control
	Wild-type from the colony
	001800 FVB/NJ
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.

---

Ordering and Purchasing Information

      Purchasing Information
      JAX^® Mice Orders
      Surgical Services

Contact Information
Orders & Technical Support
Tel: 800.422.6423 or 207.288.5845
Fax: 207.288.6150
Technical Support Email Form

Terms of Use

Terms of Use

General Terms and Conditions

For Licensing and Use Restrictions view the link(s) below:
- Use of MICE by companies or for-profit entities requires a license prior to shipping.

Contact information

General inquiries

Contracts Administration

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.”

In case of dissatisfaction for a valid reason and claimed in writing by a purchaser within ninety (90) days of receipt of MICE, products or services, The Jackson Laboratory will, at its option, provide credit or replacement for the MICE or product received or the services provided.

No Liability

In no event shall The Jackson Laboratory, 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 The Jackson Laboratory, its agents or employees. In purchasing or receiving MICE, products or services from The Jackson Laboratory, purchaser or recipient, or any party claiming by or through them, expressly releases and discharges The Jackson Laboratory from all such causes of action or damages, and further agrees to defend and indemnify The Jackson Laboratory from any costs or damages arising out of any third party claims.

MICE and biological materials 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 The Jackson Laboratory’s MICE, products and services. In addition, special terms and conditions of sale of certain MICE, products and services may be set forth separately in The Jackson Laboratory 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 The Jackson Laboratory, 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 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.