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PMID: 10359562 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

Mild spherocytosis and altered red cell ion transport in protein 4. 2-null mice.

The Journal of clinical investigation ·Vol. 103 ·No. 11 ·1999-06-00 ·Pages 1527-37

Peters LL, Jindel HK, Gwynn B, Korsgren C, John KM, Lux SE, Mohandas N, Cohen CM, Cho MR, Golan DE, Brugnara C

Abstract

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.

MeSH Terms
Animals Anion Exchange Protein 1, Erythrocyte/metabolism Blood Proteins/genetics,physiology Cations Cell Membrane Permeability Cytoskeletal Proteins Erythrocyte Membrane/metabolism,ultrastructure Erythrocytes/metabolism,ultrastructure Gene Targeting Ion Transport Male Membrane Proteins Mice Mice, Inbred C57BL Mice, Knockout Phosphorylation Potassium/metabolism Sodium/metabolism Spectrin/metabolism Spherocytosis, Hereditary/blood,etiology,genetics,metabolism
Chemicals
Anion Exchange Protein 1, Erythrocyte Blood Proteins Cations Cytoskeletal Proteins Membrane Proteins erythrocyte membrane band 4.2 protein Spectrin Sodium Potassium
Authors & Affiliations
11 authors, click to expand affiliations / ORCID
Peters L L
The Jackson Laboratory, Bar Harbor, Maine 04609, USA Department of Biomedical Research, St. Elizabeth's Medical Center, Boston, Massachusetts 02135, USA. [email protected]
Jindel H K
Gwynn B
Korsgren C
John K M
Lux S E
Mohandas N
Cohen C M
Cho M R
Golan D E
Brugnara C
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Article Info
Journal
The Journal of clinical investigation
Abbr.
J Clin Invest
ISSN
0021-9738
DOI
10.1172/JCI5766
Email
[email protected]
Published
1999-06-00
Pages
1527-37
Language
English
Region
United States
NLM ID
7802877
PMCID
PMC408368
Subset
IM
Grants
NCI NIH HHS · P30 CA034196 · United States
NHLBI NIH HHS · R01 HL032854 · United States
NHLBI NIH HHS · R01 HL055321 · United States
NHLBI NIH HHS · P01 HL032262 · United States
NIDDK NIH HHS · DK-26263 · United States
NIDDK NIH HHS · R01 DK026263 · United States
NHLBI NIH HHS · R37 HL032854 · United States
NIDDK NIH HHS · R01 DK034083 · United States
NIDDK NIH HHS · R37 DK026263 · United States
NHLBI NIH HHS · HL-55321 · United States
NIDDK NIH HHS · R01 DK050422 · United States
NIDDK NIH HHS · DK-34083 · United States
External Links
PubMed source DOI: 10.1172/JCI5766 PMC Full Text View journal details
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