PMID- 10359562
OWN - NLM
STAT- MEDLINE
DCOM- 19990804
LR  - 20181113
IS  - 0021-9738 (Print)
IS  - 0021-9738 (Linking)
VI  - 103
IP  - 11
DP  - 1999 Jun
TI  - Mild spherocytosis and altered red cell ion transport in protein 4. 2-null mice.
PG  - 1527-37
AB  - Protein 4.2 is a major component of the red blood cell (RBC) membrane skeleton.
      We used targeted mutagenesis in embryonic stem (ES) cells to elucidate protein
      4.2 functions in vivo. Protein 4. 2-null (4.2(-/-)) mice have mild hereditary
      spherocytosis (HS). Scanning electron microscopy and ektacytometry confirm loss
      of membrane surface in 4.2(-/-) RBCs. The membrane skeleton architecture is
      intact, and the spectrin and ankyrin content of 4. 2(-/-) RBCs are normal. Band 3
      and band 3-mediated anion transport are decreased. Protein 4.2(-/-) RBCs show
      altered cation content (increased K+/decreased Na+)resulting in dehydration. The 
      passive Na+ permeability and the activities of the Na-K-2Cl and K-Cl
      cotransporters, the Na/H exchanger, and the Gardos channel in 4. 2(-/-) RBCs are 
      significantly increased. Protein 4.2(-/-) RBCs demonstrate an abnormal regulation
      of cation transport by cell volume. Cell shrinkage induces a greater activation
      of Na/H exchange and Na-K-2Cl cotransport in 4.2(-/-) RBCs compared with
      controls. The increased passive Na+ permeability of 4.2(-/-) RBCs is also
      dependent on cell shrinkage. We conclude that protein 4.2 is important in the
      maintenance of normal surface area in RBCs and for normal RBC cation transport.
FAU - Peters, L L
AU  - Peters LL
AD  - The Jackson Laboratory, Bar Harbor, Maine 04609, USA Department of Biomedical
      Research, St. Elizabeth's Medical Center, Boston, Massachusetts 02135, USA.
      luanne@aeetha.jax.org
FAU - Jindel, H K
AU  - Jindel HK
FAU - Gwynn, B
AU  - Gwynn B
FAU - Korsgren, C
AU  - Korsgren C
FAU - John, K M
AU  - John KM
FAU - Lux, S E
AU  - Lux SE
FAU - Mohandas, N
AU  - Mohandas N
FAU - Cohen, C M
AU  - Cohen CM
FAU - Cho, M R
AU  - Cho MR
FAU - Golan, D E
AU  - Golan DE
FAU - Brugnara, C
AU  - Brugnara C
LA  - eng
GR  - P30 CA034196/CA/NCI NIH HHS/United States
GR  - R01 HL032854/HL/NHLBI NIH HHS/United States
GR  - R01 HL055321/HL/NHLBI NIH HHS/United States
GR  - P01 HL032262/HL/NHLBI NIH HHS/United States
GR  - DK-26263/DK/NIDDK NIH HHS/United States
GR  - R01 DK026263/DK/NIDDK NIH HHS/United States
GR  - R37 HL032854/HL/NHLBI NIH HHS/United States
GR  - R01 DK034083/DK/NIDDK NIH HHS/United States
GR  - R37 DK026263/DK/NIDDK NIH HHS/United States
GR  - HL-55321/HL/NHLBI NIH HHS/United States
GR  - R01 DK050422/DK/NIDDK NIH HHS/United States
GR  - DK-34083/DK/NIDDK NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - J Clin Invest
JT  - The Journal of clinical investigation
JID - 7802877
RN  - 0 (Anion Exchange Protein 1, Erythrocyte)
RN  - 0 (Blood Proteins)
RN  - 0 (Cations)
RN  - 0 (Cytoskeletal Proteins)
RN  - 0 (Membrane Proteins)
RN  - 0 (erythrocyte membrane band 4.2 protein)
RN  - 12634-43-4 (Spectrin)
RN  - 9NEZ333N27 (Sodium)
RN  - RWP5GA015D (Potassium)
SB  - AIM
SB  - IM
MH  - Animals
MH  - Anion Exchange Protein 1, Erythrocyte/metabolism
MH  - Blood Proteins/genetics/*physiology
MH  - Cations
MH  - Cell Membrane Permeability
MH  - Cytoskeletal Proteins
MH  - Erythrocyte Membrane/metabolism/ultrastructure
MH  - Erythrocytes/*metabolism/ultrastructure
MH  - Gene Targeting
MH  - Ion Transport
MH  - Male
MH  - Membrane Proteins
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mice, Knockout
MH  - Phosphorylation
MH  - Potassium/metabolism
MH  - Sodium/metabolism
MH  - Spectrin/metabolism
MH  - Spherocytosis, Hereditary/blood/etiology/genetics/*metabolism
PMC - PMC408368
EDAT- 1999/06/08 00:00
MHDA- 1999/06/08 00:01
CRDT- 1999/06/08 00:00
PHST- 1999/06/08 00:00 [pubmed]
PHST- 1999/06/08 00:01 [medline]
PHST- 1999/06/08 00:00 [entrez]
AID - 10.1172/JCI5766 [doi]
PST - ppublish
SO  - J Clin Invest. 1999 Jun;103(11):1527-37. doi: 10.1172/JCI5766.