Chondrodysplasia and neurological abnormalities in ATF-2-deficient mice.
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.
Reimold
A M
AM
Department of Cancer Biology, Harvard School of Public Health, Boston, Massachusetts, USA.
Grusby
M J
MJ
Kosaras
B
B
Fries
J W
JW
Mori
R
R
Maniwa
S
S
Clauss
I M
IM
Collins
T
T
Sidman
R L
RL
Glimcher
M J
MJ
Glimcher
L H
LH
D000015:Abnormalities, Multiple / Q000235:genetics; D051698:Activating Transcription Factor 2; D000818:Animals; D001921:Brain / Q000473:pathology; D002460:Cell Line; D002490:Central Nervous System / Q000002:abnormalities; D017362:Cyclic AMP Response Element-Binding Protein / Q000235:genetics / Q000502:physiology*; D019040:E-Selectin / Q000096:biosynthesis / Q000235:genetics; D005804:Genes, Lethal; D018095:Germ-Line Mutation; D006132:Growth Plate / Q000002:abnormalities; D008168:Lung / Q000378:metabolism; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D011401:Promoter Regions, Genetic; D014157:Transcription Factors
D051698:Activating Transcription Factor 2; C497106:Atf2 protein, mouse; D017362:Cyclic AMP Response Element-Binding Protein; D019040:E-Selectin; D014157:Transcription Factors