Date of Award

5-2018

Degree Type

Thesis

Degree Name

Master of Science

Department

Biology

Program

Biology

First Advisor/Chairperson

Dr. Erich Ottem

Abstract

BDNF homozygous floxed mice (BDNF lox+/+) are a transgenic mouse strain used to study the neurotrophin brain-derived neurotrophic factor (BDNF) through Cre-Lox recombination when crossed with the appropriate Cre-expressing strain. BDNF lox+/+ mice contain two artificially inserted LoxP sites located upstream and downstream from the BDNF coding region. This strain was originally described as physiologically normal and fertile by Rios et al., (2001). However, current literature lacks sufficient characterization and description of its behavioral phenotype. We utilized a three-stage behavioral protocol which included home cage monitoring observations, open-field, tail suspension, and acoustic PPI to provide a detailed behavioral phenotype for BDNF lox+/+ mice. Tail suspension protocols revealed progressive limb clasping deficits in BDNF lox+/+ mice compared to control genotypes. Importantly, the open-field test demonstrated increased locomotion in 150 d (150 day old) animals. Together these results suggest that clasping deficits are likely due to proprioceptive sensory neuropathy similar to those described by the mutant mouse strains cra1, loa and Swl (Chen et al., 2007; Dupuis et al., 2009; Zhao et al., 2016). Additionally, BDNF lox+/+ mice demonstrated increased PPI and evidence of stereotypy behaviors such as route tracing and somersaulting. We postulate that the neurological deficits presented by our data are produced by LoxP site transcriptional interference within the BDNF transcript. To support our hypothesis, future research should include quantification of BDNF expression, histological analysis of muscle spindle fibers, and cell counts of sensory and motor peripheral nerves.

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