title: Targeted deletion of alpha-adducin results in absent beta- and gamma-adducin, compensated hemolytic anemia, and lethal hydrocephalus in mice.
abstract: In the red blood cell (RBC), adducin is present primarily as tetramers of alpha- and beta-subunits at spectrin-actin junctions, or junctional complexes. Mouse RBCs also contain small amounts of gamma-adducin. Platelets contain alpha- and gamma-adducin only. Adducin functions as a barbed-end actin capping protein to regulate actin filament length and recruits spectrin to the ends of actin filaments. To further define adducin's role in vivo, we generated alpha-adducin knockout mice. alpha-Adducin is absent in all tissues examined in homozygous null mice. In RBCs, beta- and gamma-adducin are also absent, indicating that alpha-adducin is the limiting subunit in tetramer formation at the spectrin-actin junction. Similarly, gamma-adducin is absent in alpha-null platelets. alpha-Adducin-null mice display compensated hemolytic anemia with features characteristic of RBCs in hereditary spherocytosis (HS), including spherocytes with significant loss of surface area, decreased mean corpuscular volume (MCV), cell dehydration, and increased osmotic fragility. Platelets maintain their normal discoid shape, and bleeding times are normal. alpha-Adducin-null mice show growth retardation at birth and throughout adulthood. Approximately 50% develop lethal communicating hydrocephalus with striking dilation of the lateral, third, and fourth ventricles. These data indicate that adducin plays a role in RBC membrane stability and in cerebrospinal fluid homeostasis.
authors: The Jackson Laboratory, Bar Harbor, ME, USA.
authors: Raymond F
authors: RF
authors: Robledo
authors: Steven L
authors: SL
authors: Ciciotte
authors: Babette
authors: B
authors: Gwynn
authors: Kenneth E
authors: KE
authors: Sahr
authors: Diana M
authors: DM
authors: Gilligan
authors: Narla
authors: N
authors: Mohandas
authors: Luanne L
authors: LL
authors: Peters
mesh_terms: D000199:Actins / Q000235:genetics / Q000378:metabolism; D000745:Anemia, Hemolytic, Congenital / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D001792:Blood Platelets / Q000378:metabolism; D003598:Cytoskeletal Proteins / Q000235:genetics / Q000378:metabolism*; D017353:Gene Deletion; D006849:Hydrocephalus / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D051379:Mice; D018345:Mice, Knockout; D009996:Osmotic Fragility / Q000235:genetics; D020836:Protein Structure, Quaternary; D013049:Spectrin / Q000235:genetics / Q000378:metabolism; D013102:Spherocytes / Q000378:metabolism* / Q000473:pathology; D013103:Spherocytosis, Hereditary / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D000099291:Adducins
chemical_list: D000199:Actins; D003598:Cytoskeletal Proteins; D013049:Spectrin; C501062:ADD2 protein, human; D000099291:Adducins