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Title: Morphologic and genetic characterisation of the zebrafish mutant 'coma'
Author: Thomas, Swapna
Awarding Body: King's College London (University of London)
Current Institution: King's College London (University of London)
Date of Award: 2012
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Coma is an ENU-generated zebrafish mutant line. Homozygous coma larvae are immotile with heart oedema, curved body and kinky tail. Abnormality is found initially in the embryonic midbrain, hindbrain and ventral diencephalon by 28 hpf. The characterization of the mutant defect, using various GFP transgenic background revealed asymmetric folds in the midbrain and lack of differentiation of the isthmus. Further data showed that coma mutant is unable to maintain brain boundaries. No difference observed in the pattern between the coma -I- and its siblings in the whole mount in situ hybridization with MHB and hindbrain markers at 15ss suggests that ’ ,V* boundaries are properly established in the mutants but unable to be maintained. In addition to these early defects, the mutant is unable to form normal motor axons, primary reason for its lack of motility. The mutation in coma was mapped to a 5 cM interval in LG 19. Four of the eighteen SSLP markers tested were found polymorphic and linked to the mutation in a pilot study. Further mapping with the SSLP markers that are polymorphic and linked to the mutation revealed that the region of the mutated gene is around region 19:36.8 in ENSEMBL. Expression pattern analysis of candidate genes in this region together with a complementation test with a published mutant revealed that sfpq is the gene mutated in coma mutant. The protein encoded by sfpq, PSF (polypyrimidine tract-binding protein (PTB)-associated splicing factor), is a RNA processing factor that is important for RNA splicing and transcription. Our current data suggests that PSF is a protein involved in RNA processing-induced motor neurodegeneration such as ALS. Further investigation is required to understand the role of sfpq in motor axon growth and neurodegeneration.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available