Mp

The radiation induced micropinna microphthalmia (Mp) mutation, which was discovered at the Oak Ridge National Laboratory in the 1960s, has been identified as a 660 kb inversion on Chr 18 with breakpoints in 3' introns of the terminal genes: intron 62 of fibrillin 2 (Fbn2), which is transcribed from the minus strand, and intron 4 of isochorismatase domain containing 1 (Isoc1). The transcript from the resultant Fbn2/Isoc1 fusion gene joins exon 62 of the 65-exon Fbn2 directly to the last (fifth) Isoc1 exon; the predicted protein contains amino acids 1-2646 of FBN2 - which do not include the last Ca2+-binding domain and the conserved furin cleavage site - followed by 11 amino acids and a stop codon encoded by the frame-shifted Isoc1 final exon. The reverse, Isoc1/Fbn2 fusion gene produces a transcript in which a frameshift-induced stop codon in the fifth of its seven exons is predicted to result in nonsense-mediated decay; consistent with this expectation is a ~50% lower level of Isoc1/Fbn2 than of wild-type Isoc1 mRNA in developing eyes, as measured by quatitative RT-PCR. (J:203031)