DOI: 10.1152/ajpcell.1999.276.4.c788. Targeted disruption of the murine <i>Nhe1</i> locus induces ataxia, growth retardation, and seizures

Targeted disruption of the murine Nhe1 locus induces ataxia, growth retardation, and seizures

10.1152/ajpcell.1999.276.4.c788

Crossref journal-article

American Physiological Society

American Journal of Physiology-Cell Physiology (24)

Abstract

In most cells, the ubiquitously expressed Na+/H+exchanger isoform 1 (NHE1) is thought to be a primary regulator of pH homeostasis, cell volume regulation, and the proliferative response to growth factor stimulation. To study the function of NHE1 during embryogenesis when these cellular processes are very active, we targeted the Nhe1 gene by replacing the sequence encoding transmembrane domains 6 and 7 with the neomycin resistance gene. NHE activity assays on isolated acinar cells indicated that the targeted allele is functionally null. Although the absence of NHE1 is compatible with embryogenesis, Nhe1 homozygous mutants (−/−) exhibit a decreased rate of postnatal growth that is first evident at 2 wk of age. At this time, Nhe1 −/− animals also begin to exhibit ataxia and epileptic-like seizures. Approximately 67% of the −/− mutants die before weaning. Postmortem examinations frequently revealed an accumulation of a waxy particulate material inside the ears, around the eyes and chin, and on the ventral surface of the paws. Histological analysis of adult tissues revealed a thickening of the lamina propria and a slightly atrophic glandular mucosa in the stomach.

Bibliography

Bell, S. M., Schreiner, C. M., Schultheis, P. J., Miller, M. L., Evans, R. L., Vorhees, C. V., Shull, G. E., & Scott, W. J. (1999). Targeted disruption of the murine Nhe1 locus induces ataxia, growth retardation, and seizures. American Journal of Physiology-Cell Physiology, 276(4), C788âC795.

Authors 8

Sheila M. Bell (first)
Claire M. Schreiner (additional)
Patrick J. Schultheis (additional)
Marian L. Miller (additional)
Richard L. Evans (additional)
Charles V. Vorhees (additional)
Gary E. Shull (additional)
William J. Scott (additional)

References 21 Referenced 203

10.1002/(SICI)1098-2795(199806)50:2<146::AID-MRD4>3.0.CO;2-K
10.1016/S0890-6238(97)00066-X
10.1172/JCI116933
10.1016/S0092-8674(01)80016-7
10.1016/0888-7543(95)80002-4
10.1016/S0306-4522(96)00674-4
10.1074/jbc.272.36.22373
10.1016/S0021-9258(19)50428-8
10.1007/BF01872822
10.1016/0092-8674(89)90901-X
10.1002/tera.1420520308
10.1172/JCI1249
10.1016/0041-008X(90)90227-L
{'key': 'B14', 'first-page': 'A285', 'volume': '112', 'author': 'Seidler B.', 'year': '1997', 'journal-title': 'Gastroenterology'} / Gastroenterology by Seidler B. (1997)
10.1152/ajpcell.1994.266.2.C559
10.1074/jbc.270.42.25252
10.1021/bi00578a012
10.1016/S0021-9258(19)50429-X
10.1016/S0021-9258(19)50287-3
10.1016/S0021-9258(19)50288-5
10.1002/tera.1420300206

Dates

Type	When
Created	7 years, 8 months ago (Dec. 24, 2017, 5:14 p.m.)
Deposited	1 year, 2 months ago (June 17, 2024, 3:26 p.m.)
Indexed	1 month, 4 weeks ago (July 2, 2025, 2:36 p.m.)
Issued	26 years, 5 months ago (April 1, 1999)
Published	26 years, 5 months ago (April 1, 1999)
Published Print	26 years, 5 months ago (April 1, 1999)

Funders 0

None

BibTeX

@article{Bell_1999, title={Targeted disruption of the murine Nhe1 locus induces ataxia, growth retardation, and seizures}, volume={276}, ISSN={1522-1563}, url={http://dx.doi.org/10.1152/ajpcell.1999.276.4.c788}, DOI={10.1152/ajpcell.1999.276.4.c788}, number={4}, journal={American Journal of Physiology-Cell Physiology}, publisher={American Physiological Society}, author={Bell, Sheila M. and Schreiner, Claire M. and Schultheis, Patrick J. and Miller, Marian L. and Evans, Richard L. and Vorhees, Charles V. and Shull, Gary E. and Scott, William J.}, year={1999}, month=apr, pages={C788–C795} }

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