Disease relevance of Car2

• This strongly suggested that altered expression of Car2 and Ncam1 is a downstream event in placental hyperplasia [1].
• The partial protection against seizures, which CAII deficiency conferred, suggests that acidosis in the central nervous system (CNS) of the Car-2n and MldCar-2n mice, due to absence of CAII from the choroid plexus, may downregulate the activity of NMDA receptors.(ABSTRACT TRUNCATED AT 250 WORDS)[2]
• Respiratory acidosis in carbonic anhydrase II-deficient mice [3].
• Homozygosity for a null allele of the carbonic anhydrase II gene (Car2n) does not alter IOP while homozygosity for a mutation in the leptin receptor gene (Leprdb) that causes obesity and diabetes results in increased IOP [4].
• Correction of renal tubular acidosis in carbonic anhydrase II-deficient mice with gene therapy [5].

Psychiatry related information on Car2

• The effects of single and six daily doses of 40 mg or 200 mg/kg AZM on electroshock seizure threshold (EST), maximal electroshock (MES) seizure pattern, and on the activity and total amount of carbonic anhydrase II (CAII) in various subcellular fractions (cytosol, microsomes, and myelin) of cerebral cortex, cerebellum, and brainstem were assessed [6].
• Lengthened circadian period of locomotor activity is a characteristic of a congenic strain of mice carrying a nonsense mutation in exon 5 of the carbonic anhydrase II gene, car2 [7].

High impact information on Car2

• After gene therapy, CAII-deficient mice restored the ability to acidify urine after oral administration of ammonium chloride [5].
• A strain of mice of CAII deficiency due to a point mutation also manifests renal tubular acidosis [5].
• The bone resorbing cells, osteoclasts, express high levels of carbonic anhydrase II (CA II) and vacuolar H(+)-ATPase (V-ATPase) during bone resorption [8].
• Inhibition of bone resorption in vitro by antisense RNA and DNA molecules targeted against carbonic anhydrase II or two subunits of vacuolar H(+)-ATPase [8].
• These erythroid cells expressed carbonic anhydrase I and/or globin mRNA but not carbonic anhydrase II [9].

Chemical compound and disease context of Car2

• Both immunohistochemical and biochemical evidence is presented to show for the first time that carbonic anhydrase II (CA II) activity falls in the brain of mice in cuprizone (bis(cyclohexanone)oxalyldihydrazone) induced demyelination well before demyelination develops [10].
• In the flurothyl seizure model, CA II-deficient mice displayed increased resistance to clonic seizures from 32 to 90 days of age, whereas tonic-clonic seizures were suppressed at all ages [11].

Biological context of Car2

• One is a silent polymorphism found in Car2 mRNA from wild-type DBA mice, which is the strain that provided the original mutagenized chromosome [12].
• Contrary to expectations, homozygous deletion of either Car2 or Ncam1 did not result in placental phenotypes [1].
• Apart from a detailed expression analysis of both genes during normal murine placentation, we also assessed morphology of placentas that were null for Car2 or Ncam1 [1].
• Structure and exon to protein domain relationships of the mouse carbonic anhydrase II gene [13].
• Thus, except for the possible association of the 29 active site residues encoded by four exons, no obvious correspondence is seen between the regions coded by exons and the functional or secondary structural domains of the mouse CA II molecule [13].

Anatomical context of Car2

• In the neonatal mouse uterus, Car2 and Car11 mRNAs were predominantly localized in endometrial epithelial and stromal cells, respectively, whereas Car13 mRNA was detected in both epithelia and stroma [14].
• In the present study, we focused on two genes, Car2 and Ncam1, which both exhibited increased expression in interspecies and cloned hyperplastic placentas [1].
• The CA II deficiency [CA(II)D] mutation in the mouse results in structural changes in the glial cells in the CNS and in decreased susceptibility to seizures, but no detectable changes in myelin yield and ultrastructure [15].
• Up-regulation of carbonic anhydrase isozyme IV in CNS myelin of mice genetically deficient in carbonic anhydrase II [15].
• Since myelin basic protein also takes part in myelin compaction, we bred double CAII-deficient, myelin-deficient (Mld) mutant mice, in which the adults would have some compact myelin sheaths and a partial deficiency in myelin basic protein, with a view to examining oligodendrocytes and myelin sheaths in the double mutant [2].

Associations of Car2 with chemical compounds

• It is most likely that CO2 retention in these animals is due to CA II deficiency in both red blood cells and type II pneumocytes [3].
• Electrophoretic screening of (C57BL/6J x DBA/2J)F1 progeny of male mice treated with N-ethyl-N-nitrosourea revealed a mouse that lacked the paternal carbonic anhydrase II (CA II) [16].
• The possible roles of CA II and CA V in pyruvate carboxylation are discussed [17].
• Induction of new carbonic anhydrase II following treatment with acetazolamide in DBA and C57 mice [18].
• Carbonic anhydrase II-deficient mice offer a possibility to study the localization along the nephron of membrane-associated carbonic anhydrase (CA) activity without interference from the cytoplasmic enzyme [19].

Physical interactions of Car2

• I conclude that these nonconsensus Ap2-like elements and their cognitive binding protein play a major role in the expression of the CAII gene [20].
• Inhibition data of the cytosolic isozymes CA I and CA II and the membrane-bound isozyme CA IV with these inhibitors are also provided for comparison [21].

Regulatory relationships of Car2

• By comparing normal mice with CA II-deficient mice, we were able to study membrane-bound CA without influence from the ubiquitous cytoplasmic CA II [22].
• Pendrin- and vH+-ATPase-positive cells also expressed cytoplasmic CA II [23].

Other interactions of Car2

• Car9 mRNA and CA IX protein expression levels were up-regulated about 2.5- and 3.6-fold, respectively, in the stomach of the Car2-/- mice [12].
• Expression and functional analysis of genes deregulated in mouse placental overgrowth models: Car2 and Ncam1 [1].
• A Single Copy of Carbonic anhydrase 2 Restores Wild-type Circadian Period to Carbonic Anhydrase II-Deficient Mice [24].
• MATERIALS AND METHODS: We microdissected embryonic pancreases at Embryonic Days (E)9.5-11.5 and performed RT-PCR for CAII and CFTR on E9.5 whole pancreases, E10 [25].
• Carbonic anhydrase III occurred alone in some and with CA II in other sites but was often absent from CA-II-containing types of cells [26].

Analytical, diagnostic and therapeutic context of Car2

• Next we performed in situ hybridization for CAII and CFTR and immunohistochemistry for CAII on E11.5 epithelia grown for 7 days in Matrigel [25].
• Furthermore, CAII was seen by IHC and both CAII and CFTR were seen by in situ hybridization in the ducts after 7 days in Matrigel [25].
• Western blots confirmed the absence of CA II in Car-2(0) mice [27].
• The levels of both the CAII gene and its corresponding mRNA were highest by day 3 after treatment, diminishing thereafter, but remaining detectable by 1 mo [5].
• The CA II protein, which is normally expressed in most tissues, could not be detected by immunodiffusion analysis in any tissues of the CA II-deficient mice, suggesting a nonsense or a missense mutation at the Car-2 locus [16].

References