cytidine monophospho N acetylneuraminic acid hydroxylase

Summary

Gene Symbol: cytidine monophospho N acetylneuraminic acid hydroxylase
Description: cytidine monophospho-N-acetylneuraminic acid hydroxylase
Alias: cytidine monophosphate-N-acetylneuraminic acid hydroxylase, CMP-N-acetylneuraminate monooxygenase, CMP-N-acetylneuraminic acid hydroxylase, CMP-Neu5Ac hydroxylase, CMP-NeuAc hydroxylase
Species: mouse

Top Publications

  1. Hayakawa T, Satta Y, Gagneux P, Varki A, Takahata N. Alu-mediated inactivation of the human CMP- N-acetylneuraminic acid hydroxylase gene. Proc Natl Acad Sci U S A. 2001;98:11399-404 pubmed publisher
    ..It is suggested that Alu elements have played potentially important roles in genotypic and phenotypic evolution in the hominid lineage...
  2. Kavaler S, Morinaga H, Jih A, Fan W, Hedlund M, Varki A, et al. Pancreatic beta-cell failure in obese mice with human-like CMP-Neu5Ac hydroxylase deficiency. FASEB J. 2011;25:1887-93 pubmed publisher
    ..This may lend insight into the pathogenesis of type 2 diabetes in obese humans. ..
  3. Naito Y, Takematsu H, Koyama S, Miyake S, Yamamoto H, Fujinawa R, et al. Germinal center marker GL7 probes activation-dependent repression of N-glycolylneuraminic acid, a sialic acid species involved in the negative modulation of B-cell activation. Mol Cell Biol. 2007;27:3008-22 pubmed
    ..Thus, Neu5Gc is required for optimal negative regulation, and the reaction is specifically suppressed in activated B cells, i.e., germinal center B cells. ..
  4. Hedlund M, Tangvoranuntakul P, Takematsu H, Long J, Housley G, Kozutsumi Y, et al. N-glycolylneuraminic acid deficiency in mice: implications for human biology and evolution. Mol Cell Biol. 2007;27:4340-6 pubmed
    ..Adult animals also showed delayed skin wound healing. Loss of Neu5Gc in hominid ancestors approximately 2 to 3 million years ago likely had immediate and long-term consequences for human biology. ..
  5. Bousquet P, Sandvik J, Jeppesen Edin N, Krengel U. Hypothesis: Hypoxia induces de novo synthesis of NeuGc gangliosides in humans through CMAH domain substitute. Biochem Biophys Res Commun. 2018;495:1562-1566 pubmed publisher
  6. Kwon D, Chang B, Kim J. Gene expression and pathway analysis of effects of the CMAH deactivation on mouse lung, kidney and heart. PLoS ONE. 2014;9:e107559 pubmed publisher
    ..Mice bearing a human-like deletion of the Cmah gene serve as an important model for the study of abnormal pathogenesis and/or metabolism caused by the evolutionary loss of Neu5Gc synthesis in humans. ..
  7. Ma F, Deng L, Secrest P, Shi L, Zhao J, Gagneux P. A Mouse Model for Dietary Xenosialitis: ANTIBODIES TO XENOGLYCAN CAN REDUCE FERTILITY. J Biol Chem. 2016;291:18222-31 pubmed publisher
    ..These studies provide mechanistic insights on how Neu5Gc on sperm and/or endometrium combined with anti-Neu5Gc antibodies in semen and uterine fluid might contribute to unexplained human infertility. ..
  8. Buchlis G, Odorizzi P, Soto P, Pearce O, Hui D, Jordan M, et al. Enhanced T cell function in a mouse model of human glycosylation. J Immunol. 2013;191:228-37 pubmed publisher
    ..These findings in a human-like mouse model have implications for understanding the hyperimmune responses that characterize some human diseases. ..
  9. Kawano T, Koyama S, Takematsu H, Kozutsumi Y, Kawasaki H, Kawashima S, et al. Molecular cloning of cytidine monophospho-N-acetylneuraminic acid hydroxylase. Regulation of species- and tissue-specific expression of N-glycolylneuraminic acid. J Biol Chem. 1995;270:16458-63 pubmed
    ..On Southern blot analysis with the same probe, cross-hybridizing bands were detected in the human and fish genomes. ..

More Information

Publications28

  1. Ghaderi D, Springer S, Ma F, Cohen M, Secrest P, Taylor R, et al. Sexual selection by female immunity against paternal antigens can fix loss of function alleles. Proc Natl Acad Sci U S A. 2011;108:17743-8 pubmed publisher
    ..Similar circumstances existed when the CMAH null allele was polymorphic in ancestral hominins, just before the divergence of Homo from australopithecines. ..
  2. Padler Karavani V, Hurtado Ziola N, Pu M, Yu H, Huang S, Muthana S, et al. Human xeno-autoantibodies against a non-human sialic acid serve as novel serum biomarkers and immunotherapeutics in cancer. Cancer Res. 2011;71:3352-63 pubmed publisher
    ..Such xeno-autoantibodies and xeno-autoantigens have potential for novel diagnostics, prognostics, and therapeutics in human carcinomas. ..
  3. Tahara H, Ide K, Basnet N, Tanaka Y, Matsuda H, Takematsu H, et al. Immunological property of antibodies against N-glycolylneuraminic acid epitopes in cytidine monophospho-N-acetylneuraminic acid hydroxylase-deficient mice. J Immunol. 2010;184:3269-75 pubmed publisher
    ..This is the first direct demonstration of the immunogenic property of NeuGc determinants as targets of the corresponding Abs in CMAH(+/+)-to-CMAH(-/-) transplantation setting. ..
  4. Banda K, Gregg C, Chow R, Varki N, Varki A. Metabolism of vertebrate amino sugars with N-glycolyl groups: mechanisms underlying gastrointestinal incorporation of the non-human sialic acid xeno-autoantigen N-glycolylneuraminic acid. J Biol Chem. 2012;287:28852-64 pubmed publisher
    ..This human-like model can be used to elucidate specific mechanisms of Neu5Gc delivery from the gut to tissues, as well as general mechanisms of metabolism of ingested sialic acids. ..
  5. Kondo Y, Tokuda N, Fan X, Yamashita T, Honke K, Takematsu H, et al. Glycosphingolipids are not pivotal receptors for Subtilase cytotoxin in vivo: sensitivity analysis with glycosylation-defective mutant mice. Biochem Biophys Res Commun. 2009;378:179-81 pubmed publisher
    ..5 microg) of SubAB as well as wild type mice. These results indicated none of glycolipids are not pivotal receptor for SubAB in the body. ..
  6. Okerblom J, Schwarz F, Olson J, Fletes W, Ali S, Martin P, et al. Loss of CMAH during Human Evolution Primed the Monocyte-Macrophage Lineage toward a More Inflammatory and Phagocytic State. J Immunol. 2017;198:2366-2373 pubmed publisher
    ..This trade-off may have provided a selective advantage when Homo transitioned to butchery using stone tools. The findings may also explain why the Cmah-/- state alters severity in mouse models of human disease. ..
  7. Kwon D, Chang B, Kim J. MicroRNA dysregulation in liver and pancreas of CMP-Neu5Ac hydroxylase null mice disrupts insulin/PI3K-AKT signaling. Biomed Res Int. 2014;2014:236385 pubmed publisher
    ..These target miRNAs are closely associated with dysregulation of insulin/PI3K-AKT signaling, suggesting that the Cmah-null mice could be a useful model for studying diabetes. ..
  8. Deng L, Song J, Gao X, Wang J, Yu H, Chen X, et al. Host adaptation of a bacterial toxin from the human pathogen Salmonella Typhi. Cell. 2014;159:1290-9 pubmed publisher
    ..These findings provide insight into the molecular bases for Salmonella Typhi's host specificity and may help the development of therapies for typhoid fever. ..
  9. Chandrasekharan K, Yoon J, Xu Y, DeVries S, Camboni M, Janssen P, et al. A human-specific deletion in mouse Cmah increases disease severity in the mdx model of Duchenne muscular dystrophy. Sci Transl Med. 2010;2:42ra54 pubmed publisher
    ..Cmah-deficient mdx mice are a small-animal model for DMD that better approximates the human glycome and its contributions to muscular dystrophy. ..
  10. Cariappa A, Takematsu H, Liu H, Diaz S, Haider K, Boboila C, et al. B cell antigen receptor signal strength and peripheral B cell development are regulated by a 9-O-acetyl sialic acid esterase. J Exp Med. 2009;206:125-38 pubmed publisher
    ..These results describe a novel catalytic regulator of B cell signaling and underscore the crucial role of inhibitory signaling in the maintenance of immunological tolerance in the B lineage. ..
  11. Tazawa H, Irei T, Tanaka Y, Igarashi Y, Tashiro H, Ohdan H. Blockade of invariant TCR-CD1d interaction specifically inhibits antibody production against blood group A carbohydrates. Blood. 2013;122:2582-90 pubmed publisher
    ..Thus, anti-CD1d treatment might constitute a novel approach that could help in evading Ab-mediated rejection in ABO-incompatible transplant recipients. ..
  12. Pearce O, Laubli H, Verhagen A, Secrest P, Zhang J, Varki N, et al. Inverse hormesis of cancer growth mediated by narrow ranges of tumor-directed antibodies. Proc Natl Acad Sci U S A. 2014;111:5998-6003 pubmed publisher
    ..Similar findings were made in a human tumor xenograft model using a narrow range of doses of a monoclonal antibody currently in clinical use. These findings may have implications for the etiology, prevention, and treatment of cancer. ..
  13. Samraj A, Pearce O, Laubli H, Crittenden A, Bergfeld A, Banda K, et al. A red meat-derived glycan promotes inflammation and cancer progression. Proc Natl Acad Sci U S A. 2015;112:542-7 pubmed publisher
    ..This mechanism might also contribute to other chronic inflammatory processes epidemiologically associated with red meat consumption. ..
  14. Bergfeld A, Pearce O, Diaz S, Pham T, Varki A. Metabolism of vertebrate amino sugars with N-glycolyl groups: elucidating the intracellular fate of the non-human sialic acid N-glycolylneuraminic acid. J Biol Chem. 2012;287:28865-81 pubmed publisher
    ..Finally, we demonstrate that the proposed degradative pathway is partially reversible, showing that N-glycolylmannosamine and N-glycolylglucosamine (but not glycolate) can serve as precursors for biosynthesis of endogenous Neu5Gc. ..
  15. Ma X, Pan Q, Feng Y, Choudhury B, Ma Q, Gagneux P, et al. Sialylation Facilitates the Maturation of Mammalian Sperm and Affects Its Survival in Female Uterus. Biol Reprod. 2016;94:123 pubmed publisher
    ..Our results highlight the different mechanisms of increasing sialylation, which lead to the formation of the mature sperm sialome, as well as reveal the sialome's function in sperm survival within the female genital tract. ..
  16. Kwon D, Choi Y, Cho S, Park C, Seo H, Song H, et al. CMP-Neu5Ac Hydroxylase Null Mice as a Model for Studying Metabolic Disorders Caused by the Evolutionary Loss of Neu5Gc in Humans. Biomed Res Int. 2015;2015:830315 pubmed publisher
    ..The present study suggests that mice with CMAH deficiency can be taken as an important model for studying metabolic disorders in humans. ..
  17. Naito Matsui Y, Takada S, Kano Y, Iyoda T, Sugai M, Shimizu A, et al. Functional evaluation of activation-dependent alterations in the sialoglycan composition of T cells. J Biol Chem. 2014;289:1564-79 pubmed publisher
    ..Our results suggest that an activation-dependent shift from Neu5Gc to Neu5Ac and replacement of ?2,6 by ?2,3 linkages may regulate immune cell interactions at several levels. ..
  18. Koyama S, Yamaji T, Takematsu H, Kawano T, Kozutsumi Y, Suzuki A, et al. A naturally occurring 46-amino acid deletion of cytidine monophospho-N-acetylneuraminic acid hydroxylase leads to a change in the intracellular distribution of the protein. Glycoconj J. 1996;13:353-8 pubmed
    ..These data suggest that this naturally occurring 46-amino acid deletion leads to a change in the intracellular distribution of CMP-NeuAc hydroxylase, and a loss in the activity of this enzyme. ..
  19. Kawano T, Kozutsumi Y, Kawasaki T, Suzuki A. Biosynthesis of N-glycolylneuraminic acid-containing glycoconjugates. Purification and characterization of the key enzyme of the cytidine monophospho-N-acetylneuraminic acid hydroxylation system. J Biol Chem. 1994;269:9024-9 pubmed