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Targeted deletion of mouse dynein 2 light intermediate chain disrupts formation of the body axes

Rana, Amer Ahmed; (2002) Targeted deletion of mouse dynein 2 light intermediate chain disrupts formation of the body axes. Doctoral thesis (Ph.D), UCL (University College London). Green open access

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The aim of this project was to identify genes that have roles in establishing the body axes of the mouse embryo. We have carried out a screen for genes expressed in early embryonic signalling centres such as the anterior visceral endoderm and the node and its derivatives. A total of 82 single clones, which were obtained from an early mouse Endoderm cDNA library, were analysed by whole-mount in situ hybridisation on wildtype embryos from 6.5-9.5 days post-coitum. Four clones were isolated that are restricted to the tissues containing signalling centres implicated in body axis formation. From this group one clone, identified as mD2LIC, was selected for more detailed analysis based on its expression in the organiser. mD2LIC is predicted to encode a 351 amino acid protein, which contains a nucleotide binding domain and a number of phosphorylation sites. To study the role of mD2LIC in embryogenesis I have generated a mD2LIC null mutation in mouse. The mutation results in a recessive embryonic lethal phenotype in which mD2LIC-/- embryos are not detected after 11.5 dpc. Defects are first observed in the cells of the ventral node at 7.5 dpc, which have an altered shape and lack monocilia. Later defects include randomisation of the left-right axis and loss of dorsoventral patterning in the neural tube consistent with a midline defect. In addition -/- mutants also exhibit anterior truncations and display turning and ventral closure defects consistent with defective endoderm. To study the function of the gene further and to assess evolutionary conservation, I have cloned the chick, Xenopus and zebrafish homologs and have examined their expression. Furthermore, I have injected mD2LIC mRNA in X.laevis embryos, which results in an increase in gastrulation failure. In addition, attempts have been made to raise an anti-mD2LIC antibody and study the structure of the protein.

Type: Thesis (Doctoral)
Qualification: Ph.D
Title: Targeted deletion of mouse dynein 2 light intermediate chain disrupts formation of the body axes
Open access status: An open access version is available from UCL Discovery
Language: English
Additional information: Thesis digitised by ProQuest.
Keywords: Biological sciences; Embryonic signaling
URI: https://discovery.ucl.ac.uk/id/eprint/10100827
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