Generation and characterization of a cre/lox regulated transgenic zebrafish model of SBMA

This preclinical research project seeks to generate and characterize a cre/lox-regulated transgenic zebrafish model of spinal and bulbar muscular atrophy (SBMA), also known as Kennedy’s Disease. SBMA is a rare, X-linked neurodegenerative disorder caused by a mutation in the androgen receptor gene; it primarily affects males and leads to progressive loss of motor neurons and muscle dysfunction, producing symptoms such as tremors, cramping, difficulty speaking and swallowing, and eventual loss of ambulation. Motivated by both scientific this project seeks to develop a cost-effective, reproducible animal model that recapitulates disease mechanisms and accelerates discovery of therapeutic interventions.

The funded two-year effort, supported by a $151,000 grant from the National Institutes of Health, will focus on establishing a transgenic zebrafish line in which expression of the disease-associated androgen receptor can be controlled via cre/lox regulation. The zebrafish system offers practical advantages: rapid generation of data, lower maintenance costs compared with other vertebrate models, and amenability to high-throughput experimental approaches.

The researchers emphasize that disease development in the zebrafish is expected to mirror key aspects of human SBMA, enabling mechanistic studies of how mutant androgen receptor and male hormones interact to produce motor neuron degeneration. Beyond model generation, the project intends to characterize disease phenotypes at molecular, cellular, and organismal levels to ensure the model’s relevance to human pathology. A central objective is to make the model and resulting data widely available to the SBMA research community to catalyze collaboration, comparative studies, and therapeutic screening. By creating a shared resource, this project aims to shorten the timeline from basic discovery to translational testing and eventual clinical advances.

The work builds on previous efforts investigating molecular pathways that drive SBMA pathogenesis, informed by both familial experience and scientific investigation. Ultimately, the project’s goal is to provide a well-characterized, regulated zebrafish platform that can be used to test candidate therapeutics, explore disease modifiers, and deepen understanding of androgen receptor–mediated neurodegeneration. If successful, the model will help move the field forward more quickly, enabling other researchers to leverage a cost-effective preclinical system and accelerating progress toward effective therapies for men living with Kennedy’s Disease.