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 language | English (US) |
|---|---|
| Pages (from-to) | 262-265 |
| Number of pages | 4 |
| Journal | Nature |
| Volume | 379 |
| Issue number | 6562 |
| DOIs | |
| State | Published - Jan 18 1996 |
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Cite this
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 journal › Article
}
TY - JOUR
T1 - Chondrodysplasia and neurological abnormalities in ATF-2-deficient mice
AU - Reimold, Andreas M.
AU - Grusby, Michael J.
AU - Kosaras, Bela
AU - Fries, Jochen W U
AU - Mori, Ryuji
AU - Maniwa, Sokichi
AU - Clauss, Isabelle M.
AU - Collins, Tucker
AU - Sidman, Richard L.
AU - Glimcher, Melvin J.
AU - Glimcher, Laurie H.
PY - 1996/1/18
Y1 - 1996/1/18
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=13344278032&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=13344278032&partnerID=8YFLogxK
U2 - 10.1038/379262a0
DO - 10.1038/379262a0
M3 - Article
C2 - 8538792
AN - SCOPUS:13344278032
VL - 379
SP - 262
EP - 265
JO - Nature
JF - Nature
SN - 0028-0836
IS - 6562
ER -