Genetic variation in the carbonic anhydrase isozymes of macaque monkeys. II. Inheritance of red cell carbonic anhydrase levels in different carbonic anhydrase I genotypes of the pig-tailed macaque, Macaca nemestrina

The inheritance of red blood cell levels of carbonic anhydrase isozymes (CA I and CA II) has been studied in different carbonic anhydrase I genotypes of the pig-tailed macaque, Macaca nemestrina . Quantitation of CA I isozymes in a series of animals indicates that the total CA I concentration is the sum of the average effects of each CA I structural allele and that the average effects are independent of the various allelic combinations. The relative average effects were 0.32:0.95:1.0 for the CA I a , CA I b , and CA I c structural genes, respectively. It is also demonstrated that the level of CA II is related to the CA I genotypes. Multiple regression analysis demonstrated that each dose of CA I-deficiency gene present decreased the CA II concentration by approximately 30%, with this decrease in CA II level being solely related to the dose of CA I-deficiency gene and not to the level of CA I. The CA I-deficient animals produce CA I products that are similar to the common CA Ia, CA Ib, CA Ic electrophoretic types. Limited mating data indicate that the CA I components in CA I-deficient animals are inherited codominantly.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/44182/1/10528_2004_Article_BF00485544.pd

A radioimmunoassay for quantifying carbonic anhydrase isozymes in crude lysates

A radioimmunoassay was developed for quantifying each of the two genetically distinct forms of primate carbonic anhydrase, carbonic anhydrases I and II, in unpurified lysates. Under the given experimental conditions, the assay is capable of detecting a minimum of 0.025 μg of carbonic anhydrase I and 0.005 μg of carbonic anhydrase II. There is approximately 98% reproducibility upon repeated assays of a given hemolysate.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/44165/1/10528_2004_Article_BF00485779.pd

Red Cells Genetically Deficient in Carbonic Anhydrase II Have Elevated Levels of a Carbonic Anhydrase Indistinguishable from Muscle CA III a

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/71425/1/j.1749-6632.1984.tb12351.x.pd

Biochemical characterization of the human carbonic anhydrase variant CA ih Hiroshima

Some biochemical properties of a new red cell human carbonic anhydrase variant, CA Ih Hiroshima, have been determined. Evidence is presented that the amino acid substitution in the Japanese variant is not the same as the previously characterized CA Ic variant from Guam of similar electrophoretic mobility. Based on a comparison with the normal CA I isoenzyme, a proposal for the site of the amino acid substitution is presented.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/47603/1/439_2004_Article_BF00284431.pd

Quantitative genetic variation in carbonic anhydrase isozymes from tissues of the pig-tailed macaque, Macaca nemestrina

Two isozymes of carbonic anhydrase (CA I and CA II) were quantified by a radio-immunoassay in 10 different tissues of the pig-tailed macaque. There were clearly differences in relative amounts of the two isozymes, indicating a differential regulation of these two different gene products. An inherited deficiency variant reduced red cell CA I and CA II 5000-fold and 2.7-fold, respectively. In nine other tissues, CA I was reduced from approximately twofold to 110-fold, and CA II was essentially unchanged. The CA I in deficient red cells was immunochemically and electrophoretically identical to common electrophoretic variants of CA I in the pig-tailed macaque and was enzymatically active.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/44174/1/10528_2004_Article_BF00485860.pd

Characterization of the genes encoding carbonic anhydrase I of chimpanzee and gorilla: comparative analysis of 5' flanking erythroid-specific promoter sequences

The genes encoding carbonic anhydrase I (CA I) have been characterized for chimpanzee (Pan troglodytes) and gorilla (Gorilla gorilla). In addition, 44 nucleotides (nt) at the 5' end of the noncoding first exon (exon la), which is unique to the erythroid CA I mRNA, together with 188 nt of the adjacent 5' flanking regions, were sequenced for the corresponding positions of the CA I of orangutan, pigtail macaque, and squirrel monkey. When these 5' flanking regions are compared, along with those published for human and mouse CA I, they were found to contain several conserved sequences that may bind factors involved in the erythroid-specific expression of CA I. Comparisons of the human, chimpanzee, and gorilla coding and noncoding CA I sequences do not significantly deviate from a pattern of trichotomy for the evolutionary origins of these three hominoid species.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/30572/1/0000207.pd

Expression of carbonic anhydrase II (CA II) promoter-reporter fusion genes in multiple tissues of transgenic mice does not replicate normal patterns of expression indicating complexity of CA II regulation in vivo

Although the proximal, 5′ 115 bp of the human carbonic anhydrase II (CA II) gene was sufficient for expression of a reporter gene in some transfected cell lines, we found previously that 1100 bp of this promoter (or 500 bp of the mouse CA II promoter) was not sufficient for expression in transgenic mice. We have now studied the expression of linked reporter genes in mice transgenic for either (1) 11 kb of the human 5′ promoter or (2) 8 kb of the human 5′ promoter with mouse sequences from the first exon, part of the first intron (since a CpG island spans this region), and the 3′ sequences of the gene. Expression was found in both cases, but the tissue specificity was not appropriate for CA II. Although there was a difference in the sensitivity of the assays used, the first construct led to expression in many tissues, while the second construct was expressed only in spleen. These findings indicate considerable complexity of DNA control regions for in vivo CA II expression.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/44160/1/10528_2004_Article_BF00554600.pd

Genetic variation and evolution in the red cell carbonic anhydrase isozymes of macaque monkeys

The electrophoretic phenotypes of the two isozymes of red cell carbonic anhydrase, CA I and CA II, are described in nine species of macaque monkeys from southeast Asia and Japan. Twelve phenotypes of CA I, apparently under the control of seven alleles, and five phenotypes of CA II, under the control of three alleles, were found in the different macaque populations studied. Extensive electrophoretic polymorphisms of CA I were found in three species (Macaca nemestrina, Macaca speciosa , and Macaca fuscata) , and polymorphisms at the CA II locus were found in Macaca irus, Macaca mulatta , and M. nemestrina . In addition to the electrophoretic polymorphisms at the CA I locus in M. nemestrina , an inherited deficiency of CA I was also discovered in which approximately 30% of the individuals in all populations of M. nemestrina tested showed the deficient phenotype. Although the recessive gene controlling this deficiency appears to be an allele of the CA I locus, it is postulated that the CA I deficiency could also be under the control of a closely linked gene. The comparative data on the extent of genetic variation observed in the two isozymes of red cell carbonic anhydrase in macaques appear to support the concept that CA I has evolved more rapidly than CA II in mammals.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/44171/1/10528_2004_Article_BF00485644.pd

Chemical characterization of a new Japanese variant of carbonic anhydrase I, CA I Nagasaki 1 (76 Arg→Gln)

A new inherited variant of carbonic anhydrase I (CA I), designated CA I Nagasaki 1 (CA I NGS 1 ), was discovered during a survey of hemolysates from 5852 individuals from the cities of Hiroshima and Nagasaki in Japan. Analysis of the amino acid composition of a tryptic peptide from the CA I NGS 1 variant indicated that a glutaminyl residue was substituted for an arginyl residue at position 76. Heat degradation studies showed that the CA I NGS 1 variant was less stable than normal CA I. The CO 2 hydrase and esterase activities of the normal and variant carbonic anhydrases I, as well as the relative amounts of the two enzymes in heterozygotes, were similar.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/44132/1/10528_2004_Article_BF00498883.pd