1. Chondrodysplasia and neurological abnormalities in ATF-2-deficient mice
- Author
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Sokichi Maniwa, Jochen W. U. Fries, Laurie H. Glimcher, Ryuji Mori, Bela Kosaras, Andreas M. Reimold, Tucker Collins, Richard L. Sidman, Melvin J. Glimcher, Michael J. Grusby, and Isabella M. Clauss
- Subjects
Central Nervous System ,Male ,medicine.medical_specialty ,Leucine zipper ,Central nervous system ,Response element ,Hypochondroplasia ,CREB ,Cell Line ,Mice ,Germline mutation ,Internal medicine ,medicine ,Animals ,Abnormalities, Multiple ,Growth Plate ,Cyclic AMP Response Element-Binding Protein ,Promoter Regions, Genetic ,Lung ,Endochondral ossification ,Germ-Line Mutation ,Mice, Inbred BALB C ,Multidisciplinary ,Activating Transcription Factor 2 ,biology ,Brain ,medicine.disease ,Activating transcription factor 2 ,Endocrinology ,medicine.anatomical_structure ,Immunology ,biology.protein ,Genes, Lethal ,E-Selectin ,Transcription Factors - 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 CREB alpha/delta-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.
- Published
- 1996
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