Wisconsin Alumni Research Foundation

Drug Discovery & Development
Drug Discovery Development
Genetically Modified Mouse Model Displaying Abnormalities in Circadian Rhythms
WARF: P01135US

Inventors: Christopher Bradfield, Maureen Bunger, Susan Mary Moran

The Wisconsin Alumni Research Foundation (WARF) is seeking commercial partners interested in a mouse model generated by targeted mutation of a key locus in circadian regulation.
Overview
Behavioral and physiological processes in nearly all organisms display 24-hour rhythms that are controlled by a circadian pacemaker, or clock. Over the past several years, many proteins and transcription factors involved in circadian regulation have been identified, including a number of transcription factors called MOPs.
The Invention
UW-Madison researchers have developed a mouse model generated by targeted mutation of a key locus in circadian regulation, the mop3 locus. Mop3 mutant mice display characteristics indicative of complete loss of circadian clock control, including abnormal sleep patterns under conditions of 12:12 hour light:dark cycles, loss of circadian control of activity under conditions of constant darkness and reduced total activity. Other physiological consequences of the mutation include enlarged heart and liver, premature death, abnormal bone growth and decreased fertility in females.

The mop3 mutant mouse is the first to possess a single gene mutation resulting in complete loss of the circadian clock. Analyses of this mouse model also indicate that mop3 lies at the top of the hierarchy for molecular control of circadian rhythm. A surprising outgrowth of this research is that this mouse has also been shown to be a model of a common human arthropathy, known as diffuse skeletal hyperossification (DISH).
Applications
  • Development of pharmaceuticals aimed at treating disorders associated with circadian rhythm disruptions, including sleep disorders, depression, infertility and abnormalities in blood pressure control and liver metabolism
Key Benefits
  • Model possesses a single gene mutation resulting in complete loss of circadian control, making it a key system for developing drugs targeted to the MOP3 protein or gene therapies involving the mop3 gene.
  • Provides model of DISH, one of the most common forms of arthropathy in human populations
Additional Information
For More Information About the Inventors
For current licensing status, please contact Rafael Diaz at [javascript protected email address] or 608-960-9847

WARF