Hummler E, Cole TJ, Blendy JA, Ganss R, Aguzzi A, Schmid W, Beermann F, Schutz G:
Targeted mutation of the CREB gene: compensation within the CREB/ATF
family of transcription factors.
Proceedings of the National Academy of Sciences of the United States of
America 1994 Jun 7;91(12):5647-51
ABSTRACT
The cAMP response element binding protein (CREB) has been implicated
as a key regulator in the transcriptional control of many genes. To
assess the functional importance of CREB in vivo and its role in
development, we used gene targeting to generate mice with a
disruption of the CREB gene. Homozygous mutant mice appeared healthy
and exhibited no impairment of growth or development. In this report
we demonstrate that CREB and two other members of the CREB/ATF
family, cAMP response element modulation protein (CREM) and
activating transcription factor 1 (ATF1), appear to form a unique
subgroup within this extensive class of transcription factors.
Examination of CREM mRNA and protein levels in CREB mutant mice
demonstrated overexpression of CREM in all tissues examined, but no
change in ATF1 levels. These data demonstrate that CREB is not the
sole mediator of cAMP-dependent transcriptional regulation and
probably acts in concert with a specific subset of cAMP response
element-binding proteins to transduce the cAMP signal and, in its
absence, these same proteins can compensate for CREB function in
vivo.
