Cardiac-specific expression and hypertrophic upregulation of the feline Na+-Ca2+ exchanger gene H1-promoter in a transgenic mouse model

Joachim G. Müller, Yukihisa Isomatsu, Srinagesh V. Koushik, Michael O'Quinn, Lin Xu, Christiana S. Kappler, Elizabeth Hapke, Michael R. Zile, Simon Conway, Donald R. Menick

Research output: Contribution to journalArticle

26 Citations (Scopus)

Abstract

The NCX1 gene contains three promoters (H1, K1, and Br1), and as a result of alternative promoter usage and alternative splicing, there are multiple tissue-specific variants of the Na+-Ca2+ exchanger. We have proposed that for NCX1, the H1 promoter regulates expression in the heart, the K1 promoter regulates expression in the kidney, and the Br1 promoter regulates expression in the brain as well as low-level ubiquitous expression. Here, using a transgenic mouse model, we test the role of the DNA region including -1831 to 67 bp of intron 1, encompassing exon H1 of the feline NCX1 gene (NCX1H1). The NCX1H1 promoter was sufficient for driving the normal spatiotemporal pattern of NCX1 expression in cardiac development. The luciferase reporter gene was expressed in a heart-restricted pattern both in early embryos (embryonic days 8 to 14) and in later embryos (after embryonic day 14), when NCX1 is also expressed in other tissues. In the adult, no luciferase activity was detected in the kidney, liver, spleen, uterus, or skeletal muscle; minimal activity was detected in the brain; and very high levels of luciferase expression were detected in the heart. Transverse aortic constriction-operated mice showed significantly increased left ventricular mass after 7 days. In addition, there was a 2-fold upregulation of NCX1H1 promoter activity in the left ventricle in animals after 7 days of pressure overload compared with both control and sham-operated animals. This work demonstrates that the NCX1H1 promoter directs cardiac-specific expression of the exchanger in both the embryo and adult and is also sufficient for the upregulation of NCX1 in response to pressure overload.

Original languageEnglish (US)
Pages (from-to)158-164
Number of pages7
JournalCirculation Research
Volume90
Issue number2
DOIs
StatePublished - Feb 8 2002
Externally publishedYes

Fingerprint

Felidae
Luciferases
Transgenic Mice
Up-Regulation
Embryonic Structures
Genes
Kidney
Pressure
Brain
Alternative Splicing
Reporter Genes
Constriction
Introns
Uterus
Heart Ventricles
Exons
Skeletal Muscle
Spleen
Liver
DNA

Keywords

  • Na-Ca exchanger
  • Pressure-overload hypertrophy
  • Transgenic mice

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine

Cite this

Müller, J. G., Isomatsu, Y., Koushik, S. V., O'Quinn, M., Xu, L., Kappler, C. S., ... Menick, D. R. (2002). Cardiac-specific expression and hypertrophic upregulation of the feline Na+-Ca2+ exchanger gene H1-promoter in a transgenic mouse model. Circulation Research, 90(2), 158-164. https://doi.org/10.1161/hh0202.103231

Cardiac-specific expression and hypertrophic upregulation of the feline Na+-Ca2+ exchanger gene H1-promoter in a transgenic mouse model. / Müller, Joachim G.; Isomatsu, Yukihisa; Koushik, Srinagesh V.; O'Quinn, Michael; Xu, Lin; Kappler, Christiana S.; Hapke, Elizabeth; Zile, Michael R.; Conway, Simon; Menick, Donald R.

In: Circulation Research, Vol. 90, No. 2, 08.02.2002, p. 158-164.

Research output: Contribution to journalArticle

Müller, JG, Isomatsu, Y, Koushik, SV, O'Quinn, M, Xu, L, Kappler, CS, Hapke, E, Zile, MR, Conway, S & Menick, DR 2002, 'Cardiac-specific expression and hypertrophic upregulation of the feline Na+-Ca2+ exchanger gene H1-promoter in a transgenic mouse model', Circulation Research, vol. 90, no. 2, pp. 158-164. https://doi.org/10.1161/hh0202.103231
Müller, Joachim G. ; Isomatsu, Yukihisa ; Koushik, Srinagesh V. ; O'Quinn, Michael ; Xu, Lin ; Kappler, Christiana S. ; Hapke, Elizabeth ; Zile, Michael R. ; Conway, Simon ; Menick, Donald R. / Cardiac-specific expression and hypertrophic upregulation of the feline Na+-Ca2+ exchanger gene H1-promoter in a transgenic mouse model. In: Circulation Research. 2002 ; Vol. 90, No. 2. pp. 158-164.
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AU - Koushik, Srinagesh V.

AU - O'Quinn, Michael

AU - Xu, Lin

AU - Kappler, Christiana S.

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AU - Zile, Michael R.

AU - Conway, Simon

AU - Menick, Donald R.

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