Creation of a novel ETV6-Cre reporter mouse model for ETV6-related fusion protein analysis and characterization of Ink4ab/ Vav-Cre transgenic mice Lines
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Jones, Daniel William.
Creation of a novel ETV6-Cre reporter mouse model for ETV6-related fusion protein analysis and characterization of Ink4ab/ Vav-Cre transgenic mice Lines. Retrieved from
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TitleCreation of a novel ETV6-Cre reporter mouse model for ETV6-related fusion protein analysis and characterization of Ink4ab/ Vav-Cre transgenic mice Lines
Date Created2015
Other Date2015-10 (degree)
Extent1 online resource (xiii, 65 p. : ill.)
DescriptionCreation of a Novel ETV6-Cre Reporter Mouse Model for ETV6-Related Fusion Protein Analysis: The ETV6 gene is one of the most commonly targeted genes for chromosomal translocation in leukemia. ETV6 has been found to play a key role in hematopoiesis and maintenance of embryonic vascular development, yet its role in B-cell precursor acute lymphoblastic leukemia has yet to be fully determined in respect to both gene expression localization and interactions with other proteins. In this study, we focus on the creation of a novel transgenic line of ETV6-mCherry-CreERT2 mice that can be used both as a reporter for ETV6 expression and to drive ETV6-specific expression of Cre-ERT2 in mice with ETV6-related fusions using recombineering strategies. Characterization of Ink4ab/ Vav-Cre Transgenic Mice Lines: The Ink4ab genetic locus encodes for three essential proteins involved in tumor suppression, designated p15, p16, and p19 in mice. Full knockout models of this locus have been shown to exhibit accelerated tumorigenesis in multiple forms of cancer (Krimpenfort et al., 2007). By combining the Vav promoter, a promoter that first targets fetal liver hematopoietic stem cells, with a Cre-Lox system to allow full knock out of Ink4ab in only hematopoietic stem cells, we theorize the possibility of creating a hematopoietic system-based malignancy. Dissections have shown that Ink4ab+/-; Vav-Cre+ and Ink4ab-/-; Vav-Cre+ mice have splenic hyperplasia, tumor growth in both liver and spleen, and ascites in the peritoneal cavity. Peripheral blood analysis of Ink4ab-/-; Vav-Cre+ mice showed the presence of lymphoblasts, abnormal erythrocytes, and apoptotic neutrophils. Immunohistochemical staining has shown that Ink4ab-/-; Vav-Cre+ mice have increased apoptosis in T-cells, decreased mature B-cell and T-cell presence, increased cellular proliferation, deregulated cell cycle, and leukemia and lymphoma formation. These studies reveal a novel model for studying hematopoietic cell development, leukemia formation, and lymphoma formation.
NoteM.S.
NoteIncludes bibliographical references
Noteby Daniel William Jones
Genretheses, ETD graduate
Languageeng
CollectionGraduate School - New Brunswick Electronic Theses and Dissertations
Organization NameRutgers, The State University of New Jersey
RightsThe author owns the copyright to this work.
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