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Genes & Alleles

Car4;   Car4tm1Sly;

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Product Information

Strain Details

Type JAX® GEMM® Strain - Congenic Additional information on JAX® GEMM® Strains. Type JAX® GEMM® Strain - Mutant Strain Type JAX® GEMM® Strain - Targeted Mutation Species laboratory mouse Donating Investigator William Sly,   Saint Louis University Medical Center

Strain 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.

Strain Development
A tACE-CRE-neo^r 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⁺ Kitl^Sl-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.

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

Gene & Allele Details

Allele Symbol		Car4tm1Sly
Allele Name		targeted mutation 1, William S Sly
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-excicing tACE-CRE-neo cassette replaced exons 1b, 2, 3 and 9 amino acids of exon 4, sequence encoding all three active site His residues in the 146 amino acids immediately after 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. Protein was not detected in Western blot analyses of the same tissues. [MGI Ref ID J:103742]

Control Information

	Control
	000664 C57BL/6J
Considerations for Choosing Controls

Genotyping Protocols

Car4^tm1Sly

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.

Additional Web Information

Congenic Nomenclature

Research Applications

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

Neurobiology Research
Channel and Transporter Defects

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

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Price and Supply Information

Strain Name:	B6.129S1-Car4tm1Sly/J
Stock Number:	008217

 

This strain is currently Under Development for Distribution Colony.
To register your interest in this strain go to the Strain Interest Form.

Estimated Available for Sale Date:

Please note: Estimated available for sale dates are provided to keep customers better informed on strains under development. Please note that our Colony Managers routinely monitor the target date and edit it based on breeding performance and other factors. The length of time it takes to make a new strain available for sale depends on genotype, age, number of animals sent by the Donating Investigator, breeding performance, additional strain development (backcrossing, making homozygous), and anticipated demand for the strain/interest registered.

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Supply Details

Standard Supply	Under Development for Distribution Colony
Supply Notes	This strain is included in the Induced Mutant Resource Colony collection.
Licensing	See General Terms and Conditions below
Control Information	View Control Information in Strain Details.

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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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