Introductory course-based research experience for university sophomores: Using testicular-feminized mice to identify genes underlying brain sexual differentiation
Authors: Tsai Houng-Wei , Taylor Barbara 
Published: May 2024

Like many educators, we are striving to incorporate more active learning and inquiry-driven exercises into our STEM curricula. Course-based undergraduate research experiences (CUREs) have become more common in undergraduate laboratory courses in many STEM fields. Here we detail a new CURE developed in a sophomore-level undergraduate molecular neuroendocrinology course at California State University Long Beach. The course centered on the mouse model carrying testicular feminization mutation ( Tfm). This mutation, resulting from a single base deletion, produces a nonfunctional androgen receptor (AR) protein. Thus, Tfm mice are insensitive to androgen through ARs, providing an excellent model to probe the physiological role of ARs in the development of the brain and behavior. Since AR is the main mediator of androgen activity by acting as a hormonal transcription regulator, gene expression profiling has been measured in the brains of Tfm mice and normal controls to identify the potential AR-regulated genes as downstream molecular effectors. Our CURE took a similar approach, aiming to determine (1) if the selected genes were expressed differentially between the sexes and (2) if their expression could be altered by loss of AR in specific brain regions. Three broad goals of having students think, communicate, and perform like scientists were organized in the learning objectives for the CURE. All participating students (n=21) were pursuing a biology or related major, and none had any experience conducting independent laboratory research. Here students first used polymerase chain reaction (PCR) genotyping to screen the mice carrying the Tfm mutation and their sexes. They next conducted a literature search and review, through which they learned how to select databases and how to combine key words to create a productive search string for identifying the potential AR-regulated genes. Last, students performed RT-qPCR in the wild-type and Tfm mouse hypothalamus and measured sex- and AR-dependent gene expression. These modules cover not only key concepts in genetics, molecular biology, and neuroendocrinology, but also the development of methods and techniques, including DNA/RNA extraction, electrophoresis, and RT-PCR/qPCR. We designed the CURE for a semester timeline with a single three-hour laboratory section meeting once a week for 15 weeks. All modules were taught and conducted in a research laboratory containing all materials and equipment necessary for research. At the end, students constructed and presented posters on their results. To assess how well students achieved the learning goals, we administered pre- and post-course surveys. Students reported striking gains related to the learning goals, with a high degree of satisfaction. Students also perceived the improved understanding of the scientific backgrounds and methods in the CURE. This CURE course illustrates that authentic research experiences, which use complex molecular techniques, can be offered to sophomore students. The course can serve as a template to ignite students’ intellectual curiosity and improve their understanding of the scientific process by engaging them in novel research. This work was supported by the Keck Undergraduate Research Experiences (KURE) Incubator funding. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.