Balance and hearing deficits in mice with a null mutation in the gene encoding plasma membrane Ca2+-ATPase isoform 2

Peter J. Kozel, Rick A. Friedman, Lawrence C. Erway, Ebenezer N. Yamoah, Lynne H. Liu, Tara Riddle, John J. Duffy, Thomas C Doetschman, Marian L. Miller, Emma Lou Cardell, Gary E. Shull

Research output: Contribution to journalArticle

229 Citations (Scopus)

Abstract

Plasma membrane Ca2+-ATPase isoform 2 (PMCA2) exhibits a highly restricted tissue distribution, suggesting that it serves more specialized physiological functions than some of the other isoforms. A unique role in hearing is indicated by the high levels of PMCA2 expression in cochlear outer hair cells and spiral ganglion cells. To analyze the physiological role of PMCA2 we used gene targeting to produce PMCA2-deficient mice. Breeding of heterozygous mice yielded live homozygous mutant offspring. PMCA2-null mice grow more slowly than heterozygous and wild-type mice and exhibit an unsteady gait and difficulties in maintaining balance. Histological analysis of the cerebellum and inner ear of mutant and wild-type mice revealed that null mutants had slightly increased numbers of Purkinje neurons (in which PMCA2 is highly expressed), a decreased thickness of the molecular layer, an absence of otoconia in the vestibular system, and a range of abnormalities of the organ of Corti. Analysis of auditory evoked brainstem responses revealed that homozygous mutants were deaf and that heterozygous mice had a significant hearing loss. These data demonstrate that PMCA2 is required for both balance and hearing and suggest that it may be a major source of the calcium used in the formation and maintenance of otoconia.

Original languageEnglish (US)
Pages (from-to)18693-18696
Number of pages4
JournalJournal of Biological Chemistry
Volume273
Issue number30
DOIs
StatePublished - Jul 24 1998
Externally publishedYes

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Gene encoding
Calcium-Transporting ATPases
Audition
Cell membranes
Hearing
Protein Isoforms
Cell Membrane
Mutation
Genes
Otolithic Membrane
Outer Auditory Hair Cells
Neurologic Gait Disorders
Spiral Ganglion
Organ of Corti
Gene Targeting
Brain Stem Auditory Evoked Potentials
Purkinje Cells
Inner Ear
Tissue Distribution
Hearing Loss

ASJC Scopus subject areas

  • Biochemistry

Cite this

Kozel, P. J., Friedman, R. A., Erway, L. C., Yamoah, E. N., Liu, L. H., Riddle, T., ... Shull, G. E. (1998). Balance and hearing deficits in mice with a null mutation in the gene encoding plasma membrane Ca2+-ATPase isoform 2. Journal of Biological Chemistry, 273(30), 18693-18696. https://doi.org/10.1074/jbc.273.30.18693

Balance and hearing deficits in mice with a null mutation in the gene encoding plasma membrane Ca2+-ATPase isoform 2. / Kozel, Peter J.; Friedman, Rick A.; Erway, Lawrence C.; Yamoah, Ebenezer N.; Liu, Lynne H.; Riddle, Tara; Duffy, John J.; Doetschman, Thomas C; Miller, Marian L.; Cardell, Emma Lou; Shull, Gary E.

In: Journal of Biological Chemistry, Vol. 273, No. 30, 24.07.1998, p. 18693-18696.

Research output: Contribution to journalArticle

Kozel, PJ, Friedman, RA, Erway, LC, Yamoah, EN, Liu, LH, Riddle, T, Duffy, JJ, Doetschman, TC, Miller, ML, Cardell, EL & Shull, GE 1998, 'Balance and hearing deficits in mice with a null mutation in the gene encoding plasma membrane Ca2+-ATPase isoform 2', Journal of Biological Chemistry, vol. 273, no. 30, pp. 18693-18696. https://doi.org/10.1074/jbc.273.30.18693
Kozel, Peter J. ; Friedman, Rick A. ; Erway, Lawrence C. ; Yamoah, Ebenezer N. ; Liu, Lynne H. ; Riddle, Tara ; Duffy, John J. ; Doetschman, Thomas C ; Miller, Marian L. ; Cardell, Emma Lou ; Shull, Gary E. / Balance and hearing deficits in mice with a null mutation in the gene encoding plasma membrane Ca2+-ATPase isoform 2. In: Journal of Biological Chemistry. 1998 ; Vol. 273, No. 30. pp. 18693-18696.
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