Chondrodysplasia and neurological abnormalities in ATF-2-deficient mice

Andreas M. Reimold, Michael J. Grusby, Bela Kosaras, Jochen W U Fries, Ryuji Mori, Sokichi Maniwa, Isabelle M. Clauss, Tucker Collins, Richard L. Sidman, Melvin J. Glimcher, Laurie H. Glimcher

Research output: Contribution to journalArticle

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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.

Original languageEnglish (US)
Pages (from-to)262-265
Number of pages4
JournalNature
Volume379
Issue number6562
DOIs
StatePublished - Jan 18 1996

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Enchondromatosis
Transcription Factors
Response Elements
Sense Organs
Leucine Zippers
E-Selectin
Growth Plate
Germ-Line Mutation
Long-Term Potentiation
Purkinje Cells
Gait
Osteogenesis
Hearing
Central Nervous System
Brain
Growth
Genes
Mouse Hnf1b protein
Proteins

ASJC Scopus subject areas

  • General

Cite this

Reimold, A. M., Grusby, M. J., Kosaras, B., Fries, J. W. U., Mori, R., Maniwa, S., ... Glimcher, L. H. (1996). Chondrodysplasia and neurological abnormalities in ATF-2-deficient mice. Nature, 379(6562), 262-265. https://doi.org/10.1038/379262a0

Chondrodysplasia and neurological abnormalities in ATF-2-deficient mice. / Reimold, Andreas M.; Grusby, Michael J.; Kosaras, Bela; Fries, Jochen W U; Mori, Ryuji; Maniwa, Sokichi; Clauss, Isabelle M.; Collins, Tucker; Sidman, Richard L.; Glimcher, Melvin J.; Glimcher, Laurie H.

In: Nature, Vol. 379, No. 6562, 18.01.1996, p. 262-265.

Research output: Contribution to journalArticle

Reimold, AM, Grusby, MJ, Kosaras, B, Fries, JWU, Mori, R, Maniwa, S, Clauss, IM, Collins, T, Sidman, RL, Glimcher, MJ & Glimcher, LH 1996, 'Chondrodysplasia and neurological abnormalities in ATF-2-deficient mice', Nature, vol. 379, no. 6562, pp. 262-265. https://doi.org/10.1038/379262a0
Reimold AM, Grusby MJ, Kosaras B, Fries JWU, Mori R, Maniwa S et al. Chondrodysplasia and neurological abnormalities in ATF-2-deficient mice. Nature. 1996 Jan 18;379(6562):262-265. https://doi.org/10.1038/379262a0
Reimold, Andreas M. ; Grusby, Michael J. ; Kosaras, Bela ; Fries, Jochen W U ; Mori, Ryuji ; Maniwa, Sokichi ; Clauss, Isabelle M. ; Collins, Tucker ; Sidman, Richard L. ; Glimcher, Melvin J. ; Glimcher, Laurie H. / Chondrodysplasia and neurological abnormalities in ATF-2-deficient mice. In: Nature. 1996 ; Vol. 379, No. 6562. pp. 262-265.
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