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Gene Review

Add2  -  adducin 2 (beta)

Mus musculus

Synonyms: 2900072M03Rik, Add97, Beta-adducin, Erythrocyte adducin subunit beta, add97
 
 
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Disease relevance of Add2

  • A 55-kDa chimeric polypeptide is produced from the first eight exons of beta-adducin and part of the neo cassette in spleen but is not detected in peripheral RBCs or brain. beta-adducin null RBCs are osmotically fragile, spherocytic, and dehydrated compared with the wild type, resembling RBCs from patients with hereditary spherocytosis [1].
  • Mild spherocytic hereditary elliptocytosis and altered levels of alpha- and gamma-adducins in beta-adducin-deficient mice [2].
  • Combined Deletion of Mouse Dematin-Headpiece and beta-Adducin Exerts a Novel Effect on the Spectrin-Actin Junctions Leading to Erythrocyte Fragility and Hemolytic Anemia [3].
 

High impact information on Add2

  • Targeted disruption of the beta adducin gene (Add2) causes red blood cell spherocytosis in mice [1].
  • To elucidate adducin's role in vivo, we created beta-adducin null mice by gene targeting, deleting exons 9-13 [1].
  • In a comprehensive assay of gene expression, we show the ubiquitous expression of alpha- and gamma-adducins in contrast to the restricted expression of beta-adducin. beta-adducin is expressed at high levels in brain and hematopoietic tissues (bone marrow in humans, spleen in mice) [1].
  • Here we report generation and characterization of double knock-out mice lacking beta-adducin and the headpiece domain of dematin [3].
  • We have constructed a mouse strain deficient in beta-adducin having abnormal erythrocytes [4].
 

Biological context of Add2

 

Anatomical context of Add2

  • In order to assess Add2 (beta-adducin) function, its null mutation was produced in embryonic stem cells derived from 129Sv mouse and the subsequently obtained mouse mutants were backcrossed for 6 generations with C57BL/6JOlaHsd strain [5].
  • In situ hybridization for alpha- and beta-adducin demonstrates that these mRNAs are found throughout the brain, with high levels of expression in the hippocampus [8].
 

Associations of Add2 with chemical compounds

 

Regulatory relationships of Add2

 

Other interactions of Add2

  • The fact that Add2 knockout was compared with the C57BL/6JOlaHsd mouse strain, which is actually a double knockout of Snca and Mmrn1 emphasizes a need for information provided by commercial suppliers and of exact denominations of substrains used in research [5].
  • After phosphorylation at Y489, beta-adducin was translocated to the cell periphery, and colocalized with Fyn [6].
  • Hypertension in beta-adducin-deficient mice [9].
 

Analytical, diagnostic and therapeutic context of Add2

  • Western blot analysis showed that as a result of the introduced genetic modification, beta-adducin was not present in heart protein extracts from -/- mice [9].

References

  1. Targeted disruption of the beta adducin gene (Add2) causes red blood cell spherocytosis in mice. Gilligan, D.M., Lozovatsky, L., Gwynn, B., Brugnara, C., Mohandas, N., Peters, L.L. Proc. Natl. Acad. Sci. U.S.A. (1999) [Pubmed]
  2. Mild spherocytic hereditary elliptocytosis and altered levels of alpha- and gamma-adducins in beta-adducin-deficient mice. Muro, A.F., Marro, M.L., Gajović, S., Porro, F., Luzzatto, L., Baralle, F.E. Blood (2000) [Pubmed]
  3. Combined Deletion of Mouse Dematin-Headpiece and beta-Adducin Exerts a Novel Effect on the Spectrin-Actin Junctions Leading to Erythrocyte Fragility and Hemolytic Anemia. Chen, H., Khan, A.A., Liu, F., Gilligan, D.M., Peters, L.L., Messick, J., Haschek-Hock, W.M., Li, X., Ostafin, A.E., Chishti, A.H. J. Biol. Chem. (2007) [Pubmed]
  4. The erythrocyte skeletons of beta-adducin deficient mice have altered levels of tropomyosin, tropomodulin and EcapZ. Porro, F., Costessi, L., Marro, M.L., Baralle, F.E., Muro, A.F. FEBS Lett. (2004) [Pubmed]
  5. Unexpected Rescue of Alpha-synuclein and Multimerin1 Deletion in C57BL/6JOlaHsd Mice by Beta-adducin Knockout. Gajović, S., Mitrecić, D., Augustincić, L., Iaconcig, A., Muro, A.F. Transgenic Res. (2006) [Pubmed]
  6. Fyn-induced phosphorylation of beta-adducin at tyrosine 489 and its role in their subcellular localization. Gotoh, H., Okumura, N., Yagi, T., Okumura, A., Shima, T., Nagai, K. Biochem. Biophys. Res. Commun. (2006) [Pubmed]
  7. Chromosomal localization of the beta-adducin gene to mouse chromosome 6 and human chromosome 2. White, R.A., Angeloni, S.V., Pasztor, L.M. Mamm. Genome (1995) [Pubmed]
  8. Impaired synaptic plasticity and learning in mice lacking beta-adducin, an actin-regulating protein. Rabenstein, R.L., Addy, N.A., Caldarone, B.J., Asaka, Y., Gruenbaum, L.M., Peters, L.L., Gilligan, D.M., Fitzsimonds, R.M., Picciotto, M.R. J. Neurosci. (2005) [Pubmed]
  9. Hypertension in beta-adducin-deficient mice. Marro, M.L., Scremin, O.U., Jordan, M.C., Huynh, L., Porro, F., Roos, K.P., Gajovic, S., Baralle, F.E., Muro, A.F. Hypertension (2000) [Pubmed]
 
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