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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
- Phenotype
- Genes & alleles
- Genotyping
- Health & husbandry
- References
- Purchasing information
- Terms of Use
Description
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. Mating System Heterozygote x Heterozygote (Female x Male) 06-SEP-08 Species laboratory mouse Generation N21+F1 (14-JAN-09) Donating Investigator William 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 Mammalian Phenotype Terms
Mammalian Phenotype Terms
assigned by genotype
The following phenotype information may relate to a genetic background differing from this JAX® Mice strain.
Car4tm1Sly/Car4tm1Sly
involves: 129S1/Sv * C57BL/6
- lethality-postnatal
- postnatal lethality (MGI Ref ID J:103742)
- reduced survival of both male and female with a greater deficiency of females by weaning
- homozygous mice were only 38% of the number expected from Mendelian ratio
- the sex ratio was skewed in that only 31% of the homozygotes were female
- mice that survived to weaning appeared healthy, grew, and were fertile
- mating between male and female homozygous mutant mice produced small litters, and pups did not survive
This mouse can be used to support research in many areas including:
Neurobiology Research
Channel and Transporter Defects
Genes & Alleles
Gene & Allele Information
| Allele Symbol | Car4tm1Sly | ||
|---|---|---|---|
| Allele Name | targeted mutation 1, William S Sly | ||
| Allele Type | Targeted (knock-out) | ||
| Common Name(s) | CA IV KO; CAIVdl1Sws; | ||
| Mutation Made By | William Sly, Saint Louis University Medical Center | ||
| Strain of Origin | 129S1/Sv-Oca2+ Tyr+ KitlSl-J/J | ||
| ES Cell Line Name | Other (see notes) | ||
| ES Cell Line Strain | 129 | ||
| 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
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 relatedChandrashekar 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]
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]
Health & husbandry
Health & Colony Maintenance Information
Animal Health Reports
Room Number AX11
Colony Maintenance
Breeding & Husbandry When 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. Mating System Heterozygote x Heterozygote (Female x Male) 06-SEP-08 Diet Information LabDiet® 5K52/5K67
Purchasing information
Pricing, Supply Level & Notes, Controls, General Terms & Conditions
Pricing
| Pricing for USA, Canada and Mexico shipping destinations |
|
Weeks of Age Price (US dollars $) Gender Genotypes Provided Individual Mouse $243.50 Female or Male Heterozygous for Car4tm1Sly $300.70 Female or Male Homozygous for Car4tm1Sly
Pairs /Price (US dollars $) Pair Genotype $487.00 Heterozygous for Car4tm1Sly x Heterozygous for Car4tm1Sly
Additional Supply Details
| Pricing for International shipping destinations |
|
Weeks of Age Price (US dollars $) Gender Genotypes Provided Individual Mouse $316.60 Female or Male Heterozygous for Car4tm1Sly $391.00 Female or Male Homozygous for Car4tm1Sly
Pairs /Price (US dollars $) Pair Genotype $633.10 Heterozygous for Car4tm1Sly x Heterozygous for Car4tm1Sly
Additional Supply Details
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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 approximately 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 two business days following order placement. |
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| Supply Notes |
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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. | ||
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