Online citations, reference lists, and bibliographies.
← Back to Search

A Mutation Within Intron 3 Of The Pax-3 Gene Produces Aberrantly Spliced MRNA Transcripts In The Splotch (Sp) Mouse Mutant.

D. Epstein, K. Vogan, D. Trasler, P. Gros
Published 1993 · Biology, Medicine

Cite This
Download PDF
Analyze on Scholarcy
Share
The splotch (Sp) mouse mutant displays defects in neural tube closure in the form of exencephaly and spina bifida. Recently, mutations in the Pax-3 gene have been described in the radiation-induced Spr 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 Pax-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.



This paper is referenced by
10.1074/jbc.273.30.19153
Identification of a New Binding Motif for the Paired Domain of Pax-3 and Unusual Characteristics of Spacing of Bipartite Recognition Elements on Binding and Transcription Activation*
S. A. Phelan (1998)
10.1101/GAD.969302
Rescue of neural tube defects in Pax-3-deficient embryos by p53 loss of function: implications for Pax-3- dependent development and tumorigenesis.
L. Pani (2002)
10.1007/978-1-4615-1929-4_3
Pax genes as pleiotropic regulators of embryonic development
P. Tremblay (1995)
10.1002/bdra.20539
Understanding the causes and prevention of neural tube defects: Insights from the splotch mouse model.
N. Greene (2009)
10.1126/SCIENCE.272.5262.671
Molecular Pathways Controlling Heart Development
E. Olson (1996)
10.1538/EXPANIM.61.435
A novel Kit gene mutation in CF1 mice involved in the extracellular domain of the KIT protein.
S. Takabayashi (2012)
10.1101/GAD.7.10.2048
DNA sequence recognition by Pax proteins: bipartite structure of the paired domain and its binding site.
T. Czerny (1993)
10.1007/978-1-4899-1618-1_21
The Pax Family of Transcription Factors in Embryonic Development
G. Chalepakis (1995)
10.1044/HHDC11.2.7
Transgenic Mutations Affecting the Inner Ear
L. Mullen (2001)
10.1007/s10495-009-0338-6
Diabetes and apoptosis: neural crest cells and neural tube
J. Chappell (2009)
10.1002/TERA.1420500206
Early sialylation on N-CAM in splotch neural tube defect mouse embryos.
S. Neale (1994)
10.1128/MCB.16.12.6677
An alternative splicing event in the Pax-3 paired domain identifies the linker region as a key determinant of paired domain DNA-binding activity.
K. Vogan (1996)
Regulation of Sensory Neurogenesis in the Trigeminal Placode: Notch Pathway Genes, Pax3 Isoforms, and Wnt Ligands
Jason S. Adams (2012)
10.1186/s12881-015-0165-2
EPHA4 haploinsufficiency is responsible for the short stature of a patient with 2q35-q36.2 deletion and Waardenburg syndrome
C. Li (2015)
10.1074/jbc.270.36.21291
Silencer Elements Modulate the Expression of the Gene for the Neuron-Glia Cell Adhesion Molecule, Ng-CAM (*)
P. Kallunki (1995)
10.1002/(SICI)1098-1004(1997)9:2<177::AID-HUMU11>3.0.CO;2-#
Three novel PAX3 mutations observed in patients with Waardenburg syndrome type 1
H. Soejima (1997)
10.1128/MCB.15.3.1522
The PAX3-FKHR fusion protein created by the t(2;13) translocation in alveolar rhabdomyosarcomas is a more potent transcriptional activator than PAX3.
W. Fredericks (1995)
Regional Differences in Glioma: The Role of Pax3 in the Mechanisms and Cellular Origins of Brainstem Glioma
Katherine L. Misuraca (2014)
10.1002/EM.2850250612
Mutagenesis and human genetic disease: Dominant mutation frequencies and a characterization of mutational events in mice and humans
J. Favor (1995)
10.1016/S0070-2153(08)60546-3
Homeobox gene expression during development of the vertebrate brain.
J. Rubenstein (1994)
10.1093/NAR/26.20.4574
Helix 2 of the paired domain plays a key role in the regulation of DNA-binding by the Pax-3 homeodomain.
A. Fortin (1998)
Fine-scale transgenic mapping of the MyoD core enhancer: MyoD is regulated by distinct but overlapping mechanisms in myotomal and non-myotomal muscle lineages.
K. Kucharczuk (1999)
10.1002/(SICI)1097-4547(19990601)56:5<518::AID-JNR7>3.0.CO;2-8
Pax‐3 regulates neurogenesis in neural crest‐derived precursor cells
S. Koblar (1999)
Cdx-mediated co-integration of Wnt and BMP signals on a single Pax3 neural crest enhancer
Emilie Laberge Perrault (2017)
10.1007/978-1-4939-7483-2_11
Maternal Complications of Pregnancy that Affect Fetal Development
L. Longo (2018)
10.1002/DVG.20302
Generation of mice deficient for Lbx2, a gene expressed in the urogenital system, nervous system, and Pax3 dependent tissues
K. Wei (2007)
10.1111/j.1755-148X.2008.00514.x
Pigmentation PAX‐ways: the role of Pax3 in melanogenesis, melanocyte stem cell maintenance, and disease
Jennifer D. Kubic (2008)
Migration of cardiac neural crest cells in Splotch embryos.
J. Epstein (2000)
10.1093/icb/icq048
Alternative splicing in development and function of chordate endocrine systems: a focus on Pax genes.
L. Holland (2010)
Characterization of normal facial features and their association with genes
A. Toma (2014)
10.3389/fonc.2013.00252
Melanoma Biomolecules: Independently Identified but Functionally Intertwined
D. Dye (2013)
10.1016/j.mod.2008.07.003
Cardiac outflow tract septation failure in Pax3-deficient embryos is due to p53-dependent regulation of migrating cardiac neural crest
S. C. Morgan (2008)
See more
Semantic Scholar Logo Some data provided by SemanticScholar