Journal
AMERICAN JOURNAL OF HEMATOLOGY
Volume 84, Issue 6, Pages 354-361Publisher
WILEY
DOI: 10.1002/ajh.21427
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Funding
- NCI NIH HHS [P30 CA034196-24, P30 CA034196, CA34196] Funding Source: Medline
- NHLBI NIH HHS [R01 HL075714-04, R01 HL075714, HL075714] Funding Source: Medline
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In red blood cells (RBCs) adducin heterotetramers localize to the spectrin-actin junction of the peripheral membrane skeleton. We previously reported that deletion of beta-adducin results in osmotically fragile, microcytic RBCs and a phenotype of hereditary spherocytosis (HS). Notably, a-adducin was significantly reduced, while gamma-adducin, normally present in limited amounts, was increased similar to 5-fold, suggesting that a-adducin requires a heterologous binding partner for stability and function, and that gamma-adducin can partially substitute for the absence of beta-adducin. To test these assumptions we generated gamma-adducin null mice. gamma-adducin null RBCs appear normal on Wright's stained peripheral blood smears and by scanning electron microscopy. All membrane skeleton proteins examined are present in normal amounts, and all hematological parameters measured are normal. Despite a loss of similar to 70% of alpha-adducin in gamma-adducin null platelets, no bleeding defect is observed and platelet structure appears normal. Moreover, systemic blood pressure and pulse are normal in gamma-adducin null mice. gamma- and beta-adducin null mice were intercrossed to generate double null mice. Loss of gamma-adducin does not exacerbate the P-adducin null HS phenotype although the amount a-adducin is reduced to barely detectable levels. The stability of a-adducin in the absence of a heterologous binding partner varies considerably in various tissues. The amount of a-adducin is modestly reduced (similar to 15%) in the kidney, while in the spleen and brain is reduced by similar to 50% with the loss of a heterologous beta- or gamma-adducin binding partner. These results suggest that the structural properties of adducin differ significantly between erythroid and various nonerythroid cell types. Am. J. Hematol. 84:354-361, 2009. (C) 2009 Wiley-Liss, Inc.
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