| | |  | | | | Record from Web of Science® | | | | | | |
| The transcription factor NF-ATc is essential for cardiac valve formation |
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| Author(s): Ranger AM, Grusby MJ, Hodge MR, Gravallese EM, de la Brousse FC, Hoey T, Mickanin C, Baldwin HS, Glimcher LH |
| Source: NATURE Volume: 392 Issue: 6672 Pages: 186-190 Published: MAR 12 1998 |
| Times Cited: 311 References: 30 |
| Abstract: Nuclear factor of activated T cells (NF-AT) is the name of a family of four related transcription factors that may be needed for cytokine gene expression in activated lymphocytes(1-4). Here we report that mice with a targeted disruption of the NF-ATc gene show an unexpected and dramatic defect in cardiac morphogenesis, with selective absence of the aortic and pulmonary valves, leading to death in utero from congestive heart failure at days 13.5-17.5 of gestation, In contrast, tricuspid and mitral valve morphogenesis is normal, NF-ATc is the first transcription factor known to be expressed only in the endothelial cells of the heart, As in T cells, nuclear translocation of NF-ATc in cardiac endothelial cells is controlled by the calcium-regulated phosphatase calcineurin(5,6): NF-ATc remains cytoplasmic in normal embryos cultured with cyclosporin A, an inhibitor of calcineurin. Abnormal development of the cardiac valves and septae is the most frequent form of birth defect, yet few molecular regulators of valve formation are known, Our results indicate that NF-ATc may play a critical role in signal-transduction processes required for normal cardiac valve formation. |
| Document Type: Article |
| Language: English |
| Reprint Address: Glimcher, LH (reprint author), Harvard Univ, Sch Publ Hlth, Dept Canc Biol, 665 Huntington Ave, Boston, MA 02115 USA |
Addresses:
1. Harvard Univ, Sch Publ Hlth, Dept Canc Biol, Boston, MA 02115 USA
2. Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA
3. Tularik Inc, S San Francisco, CA 94080 USA
4. Childrens Hosp Philadelphia, Philadelphia, PA 19104 USA |
| Publisher: MACMILLAN MAGAZINES LTD, PORTERS SOUTH, 4 CRINAN ST, LONDON, ENGLAND N1 9XW |
| Subject Category: Multidisciplinary Sciences |
| IDS Number: ZB349 |
| ISSN: 0028-0836 |
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| | | | | | | | | Record from Web of Science® | | | | | | | | | |