Myocardium defects and ventricular hypoplasia in mice homozygous null for the Forkhead Box M1 transcription factor

Sneha Ksmiakrishna; Il Man Kim; Vladimir Petrovic; Dmitriy Malin; I. Ching Wang; Tanya V. Kalin; Lucille Meliton; You Yang Zhao; Timothy Ackerson; Yimin Qin; Asrar B. Malik; Robert H. Costa; Vladimir V. Kalinichenko

doi:10.1002/dvdy.21113

Myocardium defects and ventricular hypoplasia in mice homozygous null for the Forkhead Box M1 transcription factor

Sneha Ksmiakrishna, Il Man Kim, Vladimir Petrovic, Dmitriy Malin, I. Ching Wang, Tanya V. Kalin, Lucille Meliton, You Yang Zhao, Timothy Ackerson, Yimin Qin, Asrar B. Malik, Robert H. Costa, Vladimir V. Kalinichenko^*

^*Corresponding author for this work

Pediatrics

Research output: Contribution to journal › Article › peer-review

62 Scopus citations

Abstract

The Forkhead Box m1 (Foxm1) transcription factor is expressed in cardiomyocytes and cardiac endothelial cells during heart development. In this study, we used a novel Foxm1 -/- mouse line to demonstrate that Foxm1-deletion causes ventricular hypoplasia and diminished DNA replication and mitosis in developing cardioniyocytes. Proliferation defects in Foxm1 -/- hearts were associated with a reduced expression of Cdk1-activator Cdc25B phosphatase and NFATc3 transcription factor, and with abnormal nuclear accumulation of the Cdk-inhibitor p21^Cip1 protein. Depletion of Foxm1 levels by siRNA caused altered expression of these genes in cultured HL-1 cardiomyocytes. Endothelial-specific deletion of the Foxm1 fl/fl allele in Tie2-Cre Foxm1 fl/fl embryos did not influence heart development and cardiomyocyte proliferation. Foxm1 protein binds to the -9,259/-9,288-bp region of the endogenous mouse NFATc3 promoter, indicating that Foxm1 is a transcriptional activator of the NFATc3 gene. Foxinl regulates expression of genes essential for the proliferation of cardioniyocytes during heart development.

Original language	English (US)
Pages (from-to)	1000-1013
Number of pages	14
Journal	Developmental Dynamics
Volume	236
Issue number	4
DOIs	https://doi.org/10.1002/dvdy.21113
State	Published - Apr 2007

Keywords

Cardiomyocyte
Forkhead transcription factor
Heart development
Knockout mice
NFATc3
Trident
Winged helix DNA binding domain
p21

ASJC Scopus subject areas

Developmental Biology

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10.1002/dvdy.21113

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Ksmiakrishna, S., Kim, I. M., Petrovic, V., Malin, D., Wang, I. C., Kalin, T. V., Meliton, L., Zhao, Y. Y., Ackerson, T., Qin, Y., Malik, A. B., Costa, R. H., & Kalinichenko, V. V. (2007). Myocardium defects and ventricular hypoplasia in mice homozygous null for the Forkhead Box M1 transcription factor. Developmental Dynamics, 236(4), 1000-1013. https://doi.org/10.1002/dvdy.21113

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title = "Myocardium defects and ventricular hypoplasia in mice homozygous null for the Forkhead Box M1 transcription factor",

abstract = "The Forkhead Box m1 (Foxm1) transcription factor is expressed in cardiomyocytes and cardiac endothelial cells during heart development. In this study, we used a novel Foxm1 -/- mouse line to demonstrate that Foxm1-deletion causes ventricular hypoplasia and diminished DNA replication and mitosis in developing cardioniyocytes. Proliferation defects in Foxm1 -/- hearts were associated with a reduced expression of Cdk1-activator Cdc25B phosphatase and NFATc3 transcription factor, and with abnormal nuclear accumulation of the Cdk-inhibitor p21Cip1 protein. Depletion of Foxm1 levels by siRNA caused altered expression of these genes in cultured HL-1 cardiomyocytes. Endothelial-specific deletion of the Foxm1 fl/fl allele in Tie2-Cre Foxm1 fl/fl embryos did not influence heart development and cardiomyocyte proliferation. Foxm1 protein binds to the -9,259/-9,288-bp region of the endogenous mouse NFATc3 promoter, indicating that Foxm1 is a transcriptional activator of the NFATc3 gene. Foxinl regulates expression of genes essential for the proliferation of cardioniyocytes during heart development.",

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author = "Sneha Ksmiakrishna and Kim, {Il Man} and Vladimir Petrovic and Dmitriy Malin and Wang, {I. Ching} and Kalin, {Tanya V.} and Lucille Meliton and Zhao, {You Yang} and Timothy Ackerson and Yimin Qin and Malik, {Asrar B.} and Costa, {Robert H.} and Kalinichenko, {Vladimir V.}",

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AU - Ksmiakrishna, Sneha

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AU - Malin, Dmitriy

AU - Wang, I. Ching

AU - Kalin, Tanya V.

AU - Meliton, Lucille

AU - Zhao, You Yang

AU - Ackerson, Timothy

AU - Qin, Yimin

AU - Malik, Asrar B.

AU - Costa, Robert H.

AU - Kalinichenko, Vladimir V.

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KW - Cardiomyocyte

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Myocardium defects and ventricular hypoplasia in mice homozygous null for the Forkhead Box M1 transcription factor

Abstract

Keywords

ASJC Scopus subject areas

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