Crebbp (CREB binding protein, also known as CBP) is a protein acetyltransferase that is required for normal development. It interacts with a significant percentage of mammalian transcriptional regulatory proteins and has a CH1 domain that binds the C-terminal activation domain (C-TAD) of the hypoxia-inducible transcription factors HIF-1α and HIF-2α. This interaction is highly essential for hypoxia-responsive transcription, and is relevant to processes of glucose metabolism, angiogenesis, hematopoiesis, cell survival, invasion, and vascular tone.
These mice carry a targeted, partial, in-frame deletion of the CH1 domain in the mouse Crebbp gene (amino acids 342-393) that results in a hypomorphic protein. Western blots indicate that normal levels of a stable protein with intact HAT domain are produced. Heterozygotes on a mixed C57BL/6-129 mixed background are produced at reduced frequency and homozygotes typically die shortly after birth. C57BL/6-129 mixed background embryos examined at embryonic day 18.5 (E18.5) exhibit lung defects. Homozygous F1 hybrids generated by crossing this 129 backcrossed line (Stock No. 025531) with the same mutation on a C57BL/6-backcrossed background (see Stock No. 025172) show markedly enhanced survival to adulthood (~25% of the expected frequency), but are growth retarded and have craniofacial defects.
