Overview

Also Known As:CA II-deficient

These mice carry an ENU-induced mutation characterized by renal tubular acidosis, doubled urine output, increased urine pH and Cl^-, decreased blood pH and HCO^-₃, phosphatemia, lower plasma bicarbonate, and a smaller body size.

Genetic overview

Genetic Background	Generation
000664 C57BL/6J

Car2ⁿ

Allele Type	Gene Symbol	Gene Name
Chemically induced (ENU)	Car2	carbonic anhydrase 2

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Research Applications

Metabolism Research
Neurobiology Research
Cardiovascular Research
Developmental Biology Research
Cell Biology Research

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Base Price

Starting at:

$2,854.50 Domestic price Cryo Recovery

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Details

Detailed Description

In human, CAR2 deficiencies can result in osteopetrosis, renal tubular acidosis, impaired growth, cerebral calcification, and mental retardation. Mice homozygous for Car2<n> do not display cerebral calcification or osteopetrosis, although medial calcification of small arteries has been found in several organs, most notably the male genital tract. The phenotype of these mice includes renal tubular acidosis, doubled urine output, increased urine pH and Cl^-, decreased blood pH and HCO^-₃, phosphatemia, lower plasma bicarbonate, and a smaller body size. Despite smaller body weight, the kidneys are of normal size and plasma potassium and creatinine levels are normal. Type A and B intercalated cells of the kidney are severely depleted. Car2ⁿ homozygotes have reduced susceptibility to audiogenic and chemogenic seizures and hippocampal slices from homozygotes are more resistant to hypoxia than are those of wild type controls. Increased CAR4 levels, suggesting a compensation mechanism, have been found in oligodendrocytes and myelinated tracts. Successful liposome-delivered gene therapy has been performed on this mutant. (Lewis et al., 1988; Spicer et al., 1989; Brechue et al., 1991; Tashian, 1992; Velisek et al., 1993A and B, and 1995; Brion et al., 1994 and 1997; Breton et al.1995; Lai et al, 1998.)

Development

DBA/2J males were treated with 200mg/kg N-ethyl-N-nitrosourea then mated to C57BL/6J females10 or more weeks after treatment. Blood and kidney samples from the offspring were assayed by isoelectric focusing and a male was identified that lacked the DBA/2J derived Car2^b band. The C57BL/6J derived Car2^a band was detected. This mutant male was backcrossed to C57BL/6J. Approximately one quarter of offspring from the mating of these F1 to their mutant father were found to have no Car2 bands in any of multiple tissues assayed. In 1988 this mutation was imported into the laboratory of Dr. Jane Barker at The Jackson Laboratory from Dr. Susan Lewis at Research Triangle Institute. Dr. Barker backcrossed it further onto C57BL/6J and in 1995 C57BL/6J females were bred with homozygous B6.D2-Car2ⁿ males, then at N19, and the resulting embryos were cryopreserved. (Lewis et al., 1988; Johnson and Lewis, 1981.)

Genetics

Car2ⁿ

Allele Symbol: Car2ⁿ

Allele Name	null
Allele Type	Chemically induced (ENU)
Allele Synonym(s)	CA(II)D; CAII^-; Car2^-; Car-2⁰; Car2N
Gene Symbol and Name	Car2, carbonic anhydrase 2
Gene Synonym(s)
Strain of Origin	DBA/2J
Chromosome	3
Molecular Note	The result of ENU mutagenesis, the mutation at the Car2 locus is likely a nonsense or missense mutation. Molecular analysis shows that the mutant gene is not deleted but is transcribed. The CAR2 protein could not be detected by immunodiffusion analysis and Southern analysis indicates no detectable rearrangements or polymorphisms.

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).

autosomal recessive osteopetrosis 3

Research Areas By Phenotype

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

Genotype: Car2ⁿ related

Metabolism Research
- Enzyme Deficiency
Neurobiology Research
- Epilepsy
  - decreased susceptibility to seizures
Cardiovascular Research
- Vascular Defects
Developmental Biology Research
- Growth Defects
Cell Biology Research

Mammalian Phenotype Terms by Genotype

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

Genotype: Car2ⁿ/Car2ⁿ
involves: C57BL/6J * DBA/2J

digestive/alimentary phenotype

abnormal digestive system physiology
- bicarbonate secretory response of the duodenum to prostaglandin E2 (PGE2) is completely absent in mutants, however basal duodenal bicarbonate secretion is normal

abnormal duodenum morphology
- some mutants exhibit intraepithelial lymphocytes in the duodenum

gastric cysts
- 13% of mutants exhibit gastric cysts

stomach epithelial hyperplasia
- 50% of mutants exhibit mild gastric pit-cell hyperplasia

renal/urinary system phenotype

renal tubular acidosis
- urine has a more alkaline pH than wild-type when given tap water to drink

respiratory system phenotype

respiratory acidosis
- respiratory acidosis

growth/size/body region phenotype

postnatal growth retardation
- smaller than controls starting not later than at 2 weeks of age

homeostasis/metabolism phenotype

decreased circulating bicarbonate level

renal tubular acidosis
- urine has a more alkaline pH than wild-type when given tap water to drink

respiratory acidosis
- respiratory acidosis

mammalian phenotype

skeleton phenotype
- Normal - the prominent osteopetrosis found in humans with carbonic anhydrase II deficiency syndrome could not be detected in mice aged up to 15 months

Genotype: Car2ⁿ/Car2ⁿ
involves: DBA/2J

endocrine/exocrine gland phenotype

dilated rete testis
- rete testis dilated compared to wild-type, with equal or greater volume compared to Esr1-null mice

reproductive system phenotype

dilated efferent ductules of testis
- ductules dilated compared to wild-type, with equal or greater volume compared to Esr1-null mice

dilated rete testis
- rete testis dilated compared to wild-type, with equal or greater volume compared to Esr1-null mice

reduced male fertility
- fertility is reduced with aging

References

Additional References

Brion LP; Suarez C; Zhang H; Cammer W. 1994. Up-regulation of carbonic anhydrase isozyme IV in CNS myelin of mice genetically deficient in carbonic anhydrase II. J Neurochem 63(1):360-6PubMed: 8207439 MGI: J:18790
Lai LW; Chan DM; Erickson RP; Hsu SJ; Lien YH. 1998. Correction of renal tubular acidosis in carbonic anhydrase II-deficient mice with gene therapy. J Clin Invest 101(7):1320-5PubMed: 9525974 MGI: J:46827
Lewis SE; Erickson RP; Barnett LB; Venta PJ; Tashian RE. 1988. N-ethyl-N-nitrosourea-induced null mutation at the mouse Car-2 locus: an animal model for human carbonic anhydrase II deficiency syndrome. Proc Natl Acad Sci U S A 85(6):1962-6PubMed: 3126501 MGI: J:19268

Additional - Car2ⁿ related

Technical Support

CONTACT TECHNICAL SUPPORT

Genotyping Protocols
- Pyrosequencing:Car2-Pyro
- Genotyping resources and troubleshooting
Breeding Considerations

Car2ⁿ homozygotes are intolerant of NH4Cl in their drinking water. Homozygous females are poor breeders, often producing stillborn pups. Male homozygotes can be used for breeding.
- Additional Breeding and Husbandry Support
Citation
When using the CA II-deficient mouse strain in a publication, please cite the originating article(s) and include JAX stock #001623 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/Product	Description	Price
	Heterozygous for Car2<n>

Related Products and Services

Frozen Mouse Embryo	B6.D2-Car2<n>/J Frozen Embryos	$2595.00
Frozen Mouse Embryo	B6.D2-Car2<n>/J Frozen Embryos	$2595.00
Frozen Mouse Embryo	B6.D2-Car2<n>/J Frozen Embryos	$3373.50
Frozen Mouse Embryo	B6.D2-Car2<n>/J Frozen Embryos	$3373.50

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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. We do not guarantee breeding performance and therefore suggest that investigators order more than one breeding pair to avoid delays in their research.

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Also Known As:CA II-deficient

Genetic overview

Research Applications

Base Price

Detailed Description

Development

Car2n

Allele Symbol: Car2n

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 Phenotype

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

Genotype: Car2n related

Mammalian Phenotype Terms by Genotype

Genotype: Car2n/Car2ninvolves: C57BL/6J * DBA/2J

digestive/alimentary phenotype

renal/urinary system phenotype

respiratory system phenotype

growth/size/body region phenotype

homeostasis/metabolism phenotype

mammalian phenotype

Genotype: Car2n/Car2ninvolves: DBA/2J

endocrine/exocrine gland phenotype

reproductive system phenotype

References

Additional References

Additional - Car2n 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

Car2ⁿ

Allele Symbol: Car2ⁿ

Genotype: Car2ⁿ related

Genotype: Car2ⁿ/Car2ⁿ
involves: C57BL/6J * DBA/2J

Genotype: Car2ⁿ/Car2ⁿ
involves: DBA/2J

Additional - Car2ⁿ related