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Chondrodysplasia and neurological abnormalities in ATF-2-deficient mice

Nature volume 379, pages 262–265 (1996)Cite this article

Abstract

ACTIVATING transcription factor-2 (ATF-2) is a basic region leucine zipper protein whose DNA target sequence is the widely distributed cAMP response element (CRE). We report here that mice carrying a germline mutation in ATF-2 demonstrated unique actions of ATF-2 not duplicated by other ATF/CREB family members. Mutant mice had decreased postnatal viability and growth, with a defect in endochondral ossification at epiphyseal plates similar to human hypochondroplasia. The animals had ataxic gait, hyperactivity and decreased hearing. In the brain, there were reduced numbers of cerebellar Purkinje cells, atrophic vestibular sense organs and enlarged ventricles. Unlike CREBα/δ-deficient mice whose main defect is in long-term potentiation, the widespread abnormalities in ATF-2 mutant mice demonstrate its absolute requirement for skeletal and central nervous system development, and for maximal induction of select genes with CRE sites, such as E-selectin.

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Authors and Affiliations

  1. Department of Cancer Biology, Harvard School of Public Health,

    Andreas M. Reimold, Michael J. Grusby, Isabella M. Clauss & Laurie H. Glimcher

  2. Department of Medicine, Harvard Medical School,

    Andreas M. Reimold, Michael J. Grusby & Laurie H. Glimcher

  3. Division of Neurogenetics, New England Regional Primate Research Center, Harvard Medical School, Children's Hospital, Boston, Massachusetts, 02115, USA

    Bela Kosaras & Richard L. Sidman

  4. Vascular Research Division, Department of Pathology, Brigham and Women's Hospital and Harvard Medical School, Harvard Medical School, Children's Hospital, Boston, Massachusetts, 02115, USA

    Jochen W. U. Fries & Tucker Collins

  5. Department of Orthopaedic Surgery, Laboratory for the Study of Skeletal Disorders and Rehabilitation, Harvard Medical School, Children's Hospital, Boston, Massachusetts, 02115, USA

    Ryuji Mori, Sokichi Maniwa & Melvin J. Glimcher

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  1. Andreas M. Reimold
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Reimold, A., Grusby, M., Kosaras, B. et al. Chondrodysplasia and neurological abnormalities in ATF-2-deficient mice. Nature 379, 262–265 (1996). https://doi.org/10.1038/379262a0

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