A MUTATION WITHIN INTRON-3 OF THE PAX-3 GENE PRODUCES ABERRANTLY SPLICED MESSENGER-RNA TRANSCRIPTS IN THE SPLOTCH (SP) MOUSE MUTANT
A MUTATION WITHIN INTRON-3 OF THE PAX-3 GENE PRODUCES ABERRANTLY SPLICED MESSENGER-RNA TRANSCRIPTS IN THE SPLOTCH (SP) MOUSE MUTANT
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DOI：
10.1073/pnas.90.2.532
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发表时间：
1993-01-15
影响因子：
11.1
通讯作者：
GROS, P
中科院分区：
文献类型：
--
作者：
EPSTEIN, DJ;VOGAN, KJ;GROS, P
斑点（Sp）小鼠突变体以畸形和脊柱裂的形式显示神经管关闭缺陷。最近，在辐射诱导的Sp(r)和Sp2H等位基因中描述了Par-3基因的突变。这使得我们在原始的自发产生的Sp等位基因中检测Pax-3基因及其细胞mRNA转录物的完整性。在Sp/Sp突变体中发现了Par-3基因的复杂突变，包括在内含子3的不变3' AG剪接受体上的A -> T翻转。这种基因组突变取消了内含子3的正常剪接，导致产生四个异常剪接的mRNA转录物。其中两个Pax-3转录本利用下游外显子内的隐式3'剪接位点，产生小的缺失，破坏转录本的阅读框。第三个异常剪接事件导致外显子4的缺失，而第四个保留内含子3。这些异常剪接的mRNA转录本预计不会产生功能性的Pax-3蛋白，因此是在Sp小鼠突变体中观察到的表型的原因。
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.