Transgenic Mouse Models of Hypothyroidism

KARINNA DAVIES; CINTIA E. CITTERIO; PETER ARVAN

Simposio; Undergraduate Research Opportunity Program - Annual Spring Research Symposium; 2017

University of Michigan

Transgenic Mouse Models of HypothyroidismIntroductionHypothyroidism is a condition in which the thyroid gland does not properly make or release thyroid hormones (THs). Thyroid disease affects at least 20 million Americans and around 10% of the human population may be at risk of developing a thyroid-related disease during their lifespan. THs regulate crucial physiological functions including oxidative metabolism, heart rate and thermogenesis. Under physiological conditions TH synthesis is initiated within the precursor protein thyroglobulin (TG), a large (2746 residue) glycoprotein synthesized in thyrocytes and post-translationally iodinated on multiple monoiodotyrosine (MIT) and diiodotyrosine (DIT) residues. Chemical coupling of DIT-DIT, or MIT-DIT, within the TG protein, initiates formation of thyroxine (T4) and tri-iodothyronine (T3), respectively. The TG gene is organized in 48 exons on the mouse chromosome 15. It was found by Dr. Peter Arvan and his group found that when TG gene is disrupted in the mouse genome, there are still THs detectable in these animals. The long term objective of this project is to determine which protein/s other than TG is/are responsible for the production of TH when TG gene is knocked out.Since Dr. Peter Arvan?s laboratory researches the misfolding of proteins that lead to the development of hypothyroidism, it has different animal models of thyroid disease such as transgenic mice TG knock out and RDW (RDW is a missense mutation in TG, G2320R, which is responsible for congenital hypothyroidism in rat). Genotyping the mice is crucial in order to maintain the transgenic lines required for ongoing studies.My main responsibilities in this project include tagging the mice, taking tail biopsies, running PCR and gel electrophoresis. My goal is to identify pure TG knock out mice and propagate the transgenic mice.