Journal article
Protein 4.1R–deficient mice are viable but have erythroid membrane skeleton abnormalities
The Journal of clinical investigation, Vol.103(3), pp.331-340
02/01/1999
DOI: 10.1172/JCI3858
PMCID: PMC407893
PMID: 9927493
Abstract
A diverse family of protein 4.1R isoforms is encoded by a complex gene on human chromosome 1. Although the prototypical 80-kDa 4.1R in mature erythrocytes is a key component of the erythroid membrane skeleton that regulates erythrocyte morphology and mechanical stability, little is known about 4.1R function in nucleated cells. Using gene knockout technology, we have generated mice with complete deficiency of all 4.1R protein isoforms. These 4.1R-null mice were viable, with moderate hemolytic anemia but no gross abnormalities. Erythrocytes from these mice exhibited abnormal morphology, lowered membrane stability, and reduced expression of other skeletal proteins including spectrin and ankyrin, suggesting that loss of 4.1R compromises membrane skeleton assembly in erythroid progenitors. Platelet morphology and function were essentially normal, indicating that 4.1R deficiency may have less impact on other hematopoietic lineages. Nonerythroid 4.1R expression patterns, viewed using histochemical staining for lacZ reporter activity incorporated into the targeted gene, revealed focal expression in specific neurons in the brain and in select cells of other major organs, challenging the view that 4.1R expression is widespread among nonerythroid cells. The 4.1R knockout mice represent a valuable animal model for exploring 4.1R function in nonerythroid cells and for determining pathophysiological sequelae to 4.1R deficiency.
Details
- Title: Subtitle
- Protein 4.1R–deficient mice are viable but have erythroid membrane skeleton abnormalities
- Creators
- Zheng-Tao Shi - Life Sciences Division, Lawrence Berkeley National Laboratory, Berkeley, California 94720, USAVeena Afzal - Life Sciences Division, Lawrence Berkeley National Laboratory, Berkeley, California 94720, USABarry Coller - Life Sciences Division, Lawrence Berkeley National Laboratory, Berkeley, California 94720, USADipti Patel - Life Sciences Division, Lawrence Berkeley National Laboratory, Berkeley, California 94720, USAJoel A Chasis - Life Sciences Division, Lawrence Berkeley National Laboratory, Berkeley, California 94720, USAMarilyn Parra - Life Sciences Division, Lawrence Berkeley National Laboratory, Berkeley, California 94720, USAGloria Lee - Life Sciences Division, Lawrence Berkeley National Laboratory, Berkeley, California 94720, USAChris Paszty - Life Sciences Division, Lawrence Berkeley National Laboratory, Berkeley, California 94720, USAMary Stevens - Life Sciences Division, Lawrence Berkeley National Laboratory, Berkeley, California 94720, USALoren Walensky - Life Sciences Division, Lawrence Berkeley National Laboratory, Berkeley, California 94720, USALuanne L Peters - Life Sciences Division, Lawrence Berkeley National Laboratory, Berkeley, California 94720, USANarla Mohandas - Life Sciences Division, Lawrence Berkeley National Laboratory, Berkeley, California 94720, USAEdward Rubin - Life Sciences Division, Lawrence Berkeley National Laboratory, Berkeley, California 94720, USAJohn G Conboy - Life Sciences Division, Lawrence Berkeley National Laboratory, Berkeley, California 94720, USA
- Resource Type
- Journal article
- Publication Details
- The Journal of clinical investigation, Vol.103(3), pp.331-340
- Publisher
- American Society for Clinical Investigation
- DOI
- 10.1172/JCI3858
- PMID
- 9927493
- PMCID
- PMC407893
- ISSN
- 0021-9738
- eISSN
- 1558-8238
- Language
- English
- Date published
- 02/01/1999
- Academic Unit
- Iowa Neuroscience Institute; Immunology; Internal Medicine
- Record Identifier
- 9984070233102771
Metrics
21 Record Views