PRIMARY STRUCTURE AND DEVELOPMENTAL EXPRESSION OF FBN-1, THE MOUSE FIBRILLIN GENE

Previous studies have reported >10 kilobases of human fibrillin-1 cDNA sequence, but a consensus regarding the 5' end of the transcript rema ins to be worked out. One approach to developing a clear consensus wou ld be to search for regions of evolutionary conservation in transcript s from a related species such as mouse. As reported here, the mouse fi brillin-1 transcript encodes a highly conserved polypeptide of 2,871 a mino acids. The upstream sequence that flanks the ATG is considerably less well conserved, however. Indeed, the ATG codon (which occurs in t he context of a Kozak consensus sequence and is located just upstream of a consensus signal peptide) signals the point where human and mouse fibrillin-1 sequences cease to be nearly identical. Together, these r esults are consistent with previous efforts by Pereira et al. (Pereira , L., D'Alessio, M., Ramirez, F., Lynch, J. R., Sykes, B., Pangilinan, T., and Bonadio, J. (1993) Human Mel. Genet. 2, 961-968) to identify the human fibrillin-1 translational start site. Sequences immediately upstream of the ATG are GC-rich and devoid of TATA and CCAAT boxes, wh ich suggests that the mouse fibrillin-1 gene will be broadly expressed . A survey of expression in mouse embryo tissues is consistent with th is hypothesis and suggests two novel functions for fibrillin-associate d microfibrils in non elastic connective tissues.