POMC transgenic mice and neuron-specific promoter
OHSU # 0640
POMC neurons of the hypothalamus are critical components of the neural circuitry controlling appetite, feeding, and metabolism. In addition they modulate the activity of other hypothalamic neurons which control reproduction, thyroid hormone levels, growth hormone secretion and neuroendocrine stress responses. Genetic evidence in humans implicates the POMC gene in the regulation of weight and fat mass.
Researchers at OHSU have identified and characterized a DNA sequence upstream of the mouse POMC gene promoter that is essential for targeting gene expression specifically to POMC neurons in the hypothalamus. This is the first demonstration of DNA regulatory sequences that function as a POMC neuron-specific enhancer element, and can be used to manipulate POMC expression only in the brain. Specifically, a transgenic mouse model has been produced that is modified to incorporate the POMC promoter sequence expressing a green fluorescent protein in POMC neurons, allowing for targeting of heterologous protein expression specifically to POMC neurons.
1. Target heterologous protein expression specifically to POMC neurons in transgenic mice to study the receptor signaling in these neurons and their physiology
2. Purification of a population of hypothalamic POMC neurons as a source of RNA and protein for comparative genomic microarray and proteonomic studies
3. Identify sequence polymorphisms in the corresponding region of the human gene to correlate with body mass index and then test the functional significance in transgenic mice by gene knockins of the most suggestive mutations
4. Develop genomic screening assays to identify children at higher risk for obesity and allow early intervention
Originally generated and continually maintained on a pure inbred C57BL/6J genetic background, labelling virtually all authentic POMC neurons in the arcuate nucleus of the hypothalamus using an enhanced GFP ( EGFP) clone that produces a freely diffusable cytoplasmic protein which diffuses into the cell body, axons and dendrites of the neurons. To license POMC-eGFP mice, at a price of $20,000 per breeding pair, please place a commercial license order below.
POMC-T-Dimer Neuron-Specific Promoter
This construct and others, as described in Overstreet, L. et al (2004) J. Neurosci. 23(13) 3251-3259, are also available for licensing. For more information please contact the case manager.
|Issued||United States||7,125,979 B2|
- OHSU # 0264 — Mammalian Melanocortin Receptors and Uses (MC3)
- OHSU # 0367 — Methods and Reagents for Using Mammalian Melanocortin Receptor Agonists and Antagonists to Modulate Feeding Behavior in Animals (MC3&4)
For more information, contact:
Senior Technology Development Manager