Date of Award
Master of Science (MS)
Windsor Aguirre, Ph.D.
Talitha T. Rajah, Ph.D.
Elizabeth E. LeClair, Ph.D.
Lymphocyte cytosolic protein 1 (lcp1 or L-plastin) is a small actin-bundling protein that is typically only expressed in motile leukocytes, such as neutrophils and macrophages. However, it is also overexpressed in cancer cells, which may be related to tumor metastasis. Using CRISPR/Cas9 gene editing, our lab has created zebrafish that are genetic knockouts for lcp1 in order to better understand the relationship between L-plastin and cell motility.
Previous studies on L-plastin knockout mice have shown that the mutants have a decreased immune response, and therefore I predicted that our zebrafish mutants might have impaired development or distribution of immune cells. Other experiments have demonstrated that decreasing lcp1 in tumor cells in mice decreases the growth, invasiveness, and metastasis of cancer cells both in vitro and in vivo. Inducing tumors in the zebrafish mutant might show decreased tumor penetrance, which would further confirm the relationship between lcp1 expression and cancer. Finally, I investigated the entire transcriptome of the lcp1 mutant zebrafish embryos and compared that to the wildtype transcriptome using RNA-seq. This provides information about any genes that may be differentially expressed in the mutant in order to compensate for the lack of lcp1 mRNA.
Overall, this study aims to further characterize lcp1 mutant zebrafish in terms of their distribution of immune cells, susceptibility to tumors, as well as differences in their transcriptome in comparison to wildtype zebrafish. This data can expand on the current knowledge of the role of lcp1 in hematopoiesis and cancer, as well as adding new understanding to the dynamic between lcp1 and other genes in the transcriptome in relation to transcriptional adaptation.
Mitchell, Taylor, "lcp1 mutant zebrafish: A look at neutrophils, cancer, and gene compensation" (2018). College of Science and Health Theses and Dissertations. 332.