A MUTATION WITHIN INTRON-3 OF THE PAX-3 GENE PRODUCES ABERRANTLY SPLICED MESSENGER-RNA TRANSCRIPTS IN THE SPLOTCH (SP) MOUSE MUTANT

作者：EPSTEIN DJ; VOGAN KJ; TRASLER DG; GROS P

来源：Proceedings of the National Academy of Sciences of the United States of America, 1993, 90(2): 532-536.

DOI：10.1073/pnas.90.2.532

The splotch (Sp) mouse mutant displays defects in neural tube closure in the form of exencephaly and spina bifida. Recently, mutations in the Par-3 gene have been described in the radiation-induced Sp(r) and Sp2H alleles. This led us to examine the integrity of the Pax-3 gene and its cellular mRNA transcript in the original, spontaneously arising Sp allele. A complex mutation in the Par-3 gene including an A --> T transversion at the invariant 3' AG splice acceptor of intron 3 was identified in the Sp/Sp mutant. This genomic mutation abrogates the normal splicing of intron 3, resulting in the generation of four aberrantly spliced mRNA transcripts. Two of these Pax-3 transcripts make use of cryptic 3' splice sites within the downstream exon, generating small deletions which disrupt the reading frame of the transcripts. A third aberrant splicing event results in the deletion of exon 4, while a fourth retains intron 3. These aberrantly spliced mRNA transcripts are not expected to result in functional Pax-3 proteins and are thus responsible for the phenotype observed in the Sp mouse mutant.

• 出版日期1993-1-15