Strain Name:

B6.129S1-Car4tm1Sly/J

Stock Number:

008217

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Availability:

Cryopreserved - Ready for recovery

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Mice that are homozygous for this targeted mutation exhibit decreased sensitivity to an inhibitor, benzolamide, of pH regulation in the extracellular space in the hippocampus when compared to wildtype controls. This mutant mouse strain may be useful in studies of pH shifts that accompany neuronal activity and neuronal physiology.

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.
Specieslaboratory mouse
GenerationN20pN1
Generation Definitions
 
Donating Investigator William S Sly,   Saint Louis University Medical Center

Description
Mice that are homozygous for this targeted mutation exhibit decreased sensitivity to an inhibitor of pH regulation (benzolamide) in the extracellular space in the hippocampus when compared to wildtype controls. No gene product (mRNA or protein) is detected by RT-PCR or Western blot analysis of brain, heart, kidney, liver, and muscle tissue. Exons 1b, 2, and 3, a portion of exon 4, which encode three active-site His residues, are disrupted and results in early termination in exon 4. Fewer than expected homozygotes are produced from heterozygote crosses (with even fewer female homozygotes produced). Surviving homozygotes from heterozygote crosses are fertile when crossed to wildtype mice, normal in size and do not display any gross physical or behavioral abnormalities. Homozygous crosses produce small litters and pups do not survive. This mutant mouse strain may be useful in neuronal physiology related studies, especially those involving pH shifts that accompany neuronal activity.

Development
A tACE-CRE-neor targeting vector containing neomycin resistance, cre recombinase and the mouse Ace (angiotensin I converting enzyme (peptidyl-dipeptidase A) 1) genes was used to disrupt exons 1b, 2, 3, and a portion of exon 4. The disruption of these exons, which encode three active-site His residues, results in an early termination in exon 4. The construct was electroporated into 129S1/Sv-Oca2+ Tyr+ KitlSl-J/J derived W9.5s embryonic stem (ES) cells. Correctly targeted ES cells were injected into C57BL/6J blastocysts. The self-excising targeting vector is removed during spermatogenesis in the male chimeric animals, leaving one loxP site. The mice were then backcrossed to C57BL/6 for 20 generations before arriving at The Jackson Laboratory.

Control Information

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

Phenotype

Phenotype Information

View Related Disease (OMIM) Terms

Related Disease (OMIM) Terms provided by MGI
- Potential model based on gene homology relationships. Phenotypic similarity to the human disease has not been tested.
Retinitis Pigmentosa 17; RP17   (CA4)
View Mammalian Phenotype Terms

Mammalian Phenotype Terms provided by MGI
      assigned by genotype

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

Car4tm1Sly/Car4tm1Sly

        involves: 129S1/Sv * C57BL/6
  • mortality/aging
  • postnatal lethality
    • reduced survival of both male and female with a greater deficiency of females by weaning   (MGI Ref ID J:103742)
    • homozygous mice were only 38% of the number expected from Mendelian ratio   (MGI Ref ID J:103742)
    • the sex ratio was skewed in that only 31% of the homozygotes were female   (MGI Ref ID J:103742)
    • mice that survived to weaning appeared healthy, grew, and were fertile   (MGI Ref ID J:103742)
    • mating between male and female homozygous mutant mice produced small litters, and pups did not survive   (MGI Ref ID J:103742)
View Research Applications

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

Neurobiology Research
Channel and Transporter Defects

Genes & Alleles

Gene & Allele Information provided by MGI

 
Allele Symbol Car4tm1Sly
Allele Name targeted mutation 1, William S Sly
Allele Type Targeted (Null/Knockout)
Common Name(s) CA IV KO; CAIVdl1Sws;
Mutation Made By William Sly,   Saint Louis University Medical Center
Strain of Origin129S1/Sv-Oca2+ Tyr+ KitlSl-J/J
ES Cell Line NameOther (see notes)
ES Cell Line Strain129
Gene Symbol and Name Car4, carbonic anhydrase 4
Chromosome 11
Gene Common Name(s) AW456718; CA IV; CAIV; Ca4; RP17; expressed sequence AW456718;
General Note ES cell line = W9.5s
Molecular Note The self-excising tACE-CRE-neo cassette replaced exons 1b, 2, 3, and 9 amino acids of exon 4. This sequence encodes all three active site His residues in the 146 amino acids of the protein that immediately follow the signal sequence. The resulting frameshift produced an early termination in exon 4. Absence of transcript was confirmed by RT-PCR of mutant brain, heart, kidney and muscle. Western blot analyses of the same tissues did not detect protein. [MGI Ref ID J:103742]

Genotyping

Genotyping Information

Genotyping Protocols

Car4tm1Sly, Standard PCR


Helpful Links

Genotyping resources and troubleshooting

References

References provided by MGI

Selected Reference(s)

Shah GN; Ulmasov B; Waheed A; Becker T; Makani S; Svichar N; Chesler M; Sly WS. 2005. Carbonic anhydrase IV and XIV knockout mice: roles of the respective carbonic anhydrases in buffering the extracellular space in brain. Proc Natl Acad Sci U S A 102(46):16771-6. [PubMed: 16260723]  [MGI Ref ID J:103742]

Additional References

Car4tm1Sly related

Chandrashekar J; Yarmolinsky D; von Buchholtz L; Oka Y; Sly W; Ryba NJ; Zuker CS. 2009. The taste of carbonation. Science 326(5951):443-5. [PubMed: 19833970]  [MGI Ref ID J:153753]

Hallerdei J; Scheibe RJ; Parkkila S; Waheed A; Sly WS; Gros G; Wetzel P; Endeward V. 2010. T tubules and surface membranes provide equally effective pathways of carbonic anhydrase-facilitated lactic acid transport in skeletal muscle. PLoS One 5(12):e15137. [PubMed: 21179203]  [MGI Ref ID J:167710]

Ogilvie JM; Ohlemiller KK; Shah GN; Ulmasov B; Becker TA; Waheed A; Hennig AK; Lukasiewicz PD; Sly WS. 2007. Carbonic anhydrase XIV deficiency produces a functional defect in the retinal light response. Proc Natl Acad Sci U S A 104(20):8514-9. [PubMed: 17485676]  [MGI Ref ID J:121839]

Scheibe RJ; Gros G; Parkkila S; Waheed A; Grubb JH; Shah GN; Sly WS; Wetzel P. 2006. Expression of membrane-bound carbonic anhydrases IV, IX, and XIV in the mouse heart. J Histochem Cytochem 54(12):1379-91. [PubMed: 16924128]  [MGI Ref ID J:116277]

Scheibe RJ; Mundhenk K; Becker T; Hallerdei J; Waheed A; Shah GN; Sly WS; Gros G; Wetzel P. 2008. Carbonic anhydrases IV and IX: subcellular localization and functional role in mouse skeletal muscle. Am J Physiol Cell Physiol 294(2):C402-12. [PubMed: 18003750]  [MGI Ref ID J:132205]

Schneider HP; Alt MD; Klier M; Spiess A; Andes FT; Waheed A; Sly WS; Becker HM; Deitmer JW. 2013. GPI-anchored carbonic anhydrase IV displays both intra- and extracellular activity in cRNA-injected oocytes and in mouse neurons. Proc Natl Acad Sci U S A 110(4):1494-9. [PubMed: 23297198]  [MGI Ref ID J:193715]

Wandernoth PM; Raubuch M; Mannowetz N; Becker HM; Deitmer JW; Sly WS; Wennemuth G. 2010. Role of carbonic anhydrase IV in the bicarbonate-mediated activation of murine and human sperm. PLoS One 5(11):e15061. [PubMed: 21124840]  [MGI Ref ID J:167319]

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

Animal Health Reports

Production of mice from cryopreserved embryos or sperm occurs in a maximum barrier room, G200.

Colony Maintenance

Breeding & HusbandryWhen maintaining a live colony, these mice can be bred as female heterozygotes and male homozygotes. Fewer than expected homozygotes are produced from heterozygote crosses (with even fewer female homozygotes produced). Homozygous crosses produce small litters and pups do not survive.

Pricing and Purchasing

Pricing, Supply Level & Notes, Controls


Pricing for USA, Canada and Mexico shipping destinations View International Pricing

Cryopreserved

Cryopreserved Mice - Ready for Recovery

Price (US dollars $)
Cryorecovery* $2140.00
Animals Provided

At least two mice that carry the mutation (if it is a mutant strain) will be provided. Their genotypes may not reflect those discussed in the strain description. Please inquire for possible genotypes and see additional details below.

Standard Supply

Cryopreserved. Ready for recovery. Please refer to pricing and supply notes on the strain data sheet for further information.

Supply Notes

  • Cryorecovery - Standard.
    Progeny testing is not required.

    The average number of mice provided from recovery of our cryopreserved strains is 10. The total number of animals provided, their gender and genotype will vary. We will fulfill your order by providing at least two pair of mice, at least one animal of each pair carrying the mutation of interest. Please inquire if larger numbers of animals with specific genotype and genders are needed. Animals typically ship between 10 and 14 weeks from the date of your order. If a second cryorecovery is needed in order to provide the minimum number of animals, animals will ship within 25 weeks. IMPORTANT NOTE: The genotypes of 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 about possible genotypes which will be recovered for this specific strain. The Jackson Laboratory 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. For more information on Dedicated Supply, please contact JAX® Services, Tel: 1-800-422-6423 (from U.S.A., Canada or Puerto Rico only) or 1-207-288-5845 (from any location).

Pricing for International shipping destinations View USA Canada and Mexico Pricing

Cryopreserved

Cryopreserved Mice - Ready for Recovery

Price (US dollars $)
Cryorecovery* $2782.00
Animals Provided

At least two mice that carry the mutation (if it is a mutant strain) will be provided. Their genotypes may not reflect those discussed in the strain description. Please inquire for possible genotypes and see additional details below.

Standard Supply

Cryopreserved. Ready for recovery. Please refer to pricing and supply notes on the strain data sheet for further information.

Supply Notes

  • Cryorecovery - Standard.
    Progeny testing is not required.

    The average number of mice provided from recovery of our cryopreserved strains is 10. The total number of animals provided, their gender and genotype will vary. We will fulfill your order by providing at least two pair of mice, at least one animal of each pair carrying the mutation of interest. Please inquire if larger numbers of animals with specific genotype and genders are needed. Animals typically ship between 10 and 14 weeks from the date of your order. If a second cryorecovery is needed in order to provide the minimum number of animals, animals will ship within 25 weeks. IMPORTANT NOTE: The genotypes of 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 about possible genotypes which will be recovered for this specific strain. The Jackson Laboratory 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. For more information on Dedicated Supply, please contact JAX® Services, Tel: 1-800-422-6423 (from U.S.A., Canada or Puerto Rico only) or 1-207-288-5845 (from any location).

View USA Canada and Mexico Pricing View International Pricing

Standard Supply

Cryopreserved. Ready for recovery. Please refer to pricing and supply notes on the strain data sheet for further information.

Control Information

  Control
   Wild-type from the colony
   000664 C57BL/6J
 
  Considerations for Choosing Controls
  Control Pricing Information for Genetically Engineered Mutant Strains.
 

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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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