The following is a group of neurology mouse models may be licensed for research and screeening of novel therapies in the areas of stress/anxiety, drug/alcohol addiction, neuroendocrine-based, and neurodegenerative diseases:

• FLAGMOR transgenic: Expresses an epitope-tagged m-opioid receptor targeted to catecholamine neurons. Useful for the combined study of acute signaling through the activation of GIRK channels, desensitization, and receptor trafficking within the brain.
• Corticotrophin-releasing Hormone Receptor 2 (CRH R2) knockout for studying mental disorders, including stress/anxiety, major depression and, more recently, Alzheimer's disease has been associated with dysregulation of CRH. CRH-R2 may play an important role in maintaining and terminating stess response during the recovery phase.
• Corticotrophin-releasing Hormone Receptor 1 and 2 (CRH R1/R2) double knockout: CRH R1 and CRH R2 do not have overlapping functions and when there is loss in one or the other there is impairment of the hypothalamic-pituitary-adrenal (HPA) system function. This model serves as an important tool for investigating the HPA regulationand how it affects cognitive, metabolic and anxiety-related behaviors.
• SK1: is a small-conductance Ca2+-activated postassium channel. Most of the higher brain regions show expression of SK1 channels. SK1 mRNA is observed in very few subcortical areas. This knockout model maybe used for the study of neuron excitation, synaptic plasticity, and hippocampus-dependent processes.
• SK2: is a small-conductance Ca2+-activated potassium channel expressed in the higher brain regions as well as in the thalamus and in the reticular formation, but not in monoaminergic systems. High levels of SK2 have been observed in the liver and heart. This knockout model maybe used for the study of neuron excitation, synaptic plasticity, and hippocampus-dependent processes.
• SK3: is a small-conductance Ca2+-activated potassium channel. Some examples of disorders in which SK3 plays a role include: sleep apnea or sudden infant death syndrome, dopamine related disorders (Parkinson's), depression, bipolar disorder, memory loss associated with aging, anorexia nervosa, high blood pressue, breast cancer metastasis, and urinary bladder infection.
• Dopamine receptor, D2 receptor knockout: maybe used alone or in combination with the D4 receptor knockout for the study of dopamine in drug/alcohol addictions and other neurological disorders.
• Dopamine receptor, D4 receptor knockout: maybe used alone or in combination with the D2 receptor knockout for the study of dopamine in drug/alcohol addictions as well as other neurological disorders.
• Type1 adenylcyclase knockout: Production of cAMP by adenylyl cyclase (AC) provides an important mechanism for regulation of neuronal physiology. Targeted inactivation of AC1 results in defective spacial learning, motor coordination, and hippocampal and cerebellar long-term potentiation and thus this knockout model may be used to investigate the multiple pathways that regulate cAMP and treatments for memory loss.
• Type 3 adenylyl cyclase knockout: is a useful animal for screening for drugs that modulate olfaction and obesity related disorders. Electrophysological studyes demonstrated that anosmia toward both IP3- and cAMP-generating ordorants, despite the presence of other adenylyl cyclases in olfacotry cilia.
• Type1 -type8 adenylcyclase double knockout: model for development of treatments for long-term potentiatio, and use of targets type 1 or 8 adenylyl cyclase sites to modulate synaptic response.
• Dopamine-hydroxylase /Galanin transgenic: displays cognitive and neurochemical deficits characteristic of Alzheimer's disease.
• Neuropeptide Y5 (NPY5) receptor knockout: NPY5 is a neuromodulator abundantly expressed in the brain and has been implicated in the regulation of food intake and body weight. Pharmacological data suggests that NPY's stimulatory effect on appetite is transduced by GPCR. This model provides a system for the study of feed regulation and obsesity.
• Neuropeptide Y receptor knockout: neuropeptide Y receptor modulates voluntary ethanol consumption, feeding behavior, mood, cerebrocortical excitability, hypothalamic-pituitary signaling, cardiovascular physiology and sympathetic function. This model provides a system to study drug/alcohol addiction, feed regulation and mood.
• Zinc transporter-3 knockout: A system for investigating the roles of synaptic vesicle zinc in zinc-enriched neurons, because they exhibit normal brain morphology and the lesion is very specific. For example, the zinc that is bound to the protein is still present and histochemically-reactive zinc in organs outside of the central nervous system is unaffected by the removal of Zn transporter 3.
• Transient potential V3 (TRPV3): TRPV3 null mice have defective responses to innocuous and noxious heat but not in other sensory modalities. This model serves as a useful tool for the study of thermo-sensation.
• VgEcR-RXR: A modified ecdysone receptor (VgEcR) and the retinoid X receptor (RXR) transgenic mouse serves as a system for examiing ecdysone-regulated gene expression in mammalian cells with implications for neuronal function, lipid metabolism, signaling, cell cycle regulation, embryonic development, cancer and apoptosis.
• Attention Deficit Disorder/ Attention Deficit Hyperactivity Disorder (ADD/ADHD): Transgenic mouse model at a nuclear hormone receptor locus having utility as a model system for studying ADD/ADHD.
• Tlx knockout: may be employed to identify compounds or ways to overcome loss of Tlx activity having implications for neurodegenerative diseases, visual disorders, reversing age-related depopulation, rescuing degenerated, and promoting generation of and maintainance of neural cells or neural stem cells.
• Corticotropin-releasing Factor overexpression transgenic: this patented CRF overproduction model (US patents 6023011 and 6166287) provides a valuable tool for the investigation of long term effects of CRF excess such as dysregulation in the CNS and Crushing's syndrome. These micemay also be used to screen compounds that modulate corticotrophin
• ErbB4 knockout: provides a important tool for studying cardiac muscle differentiation and axon guidane in the CNS as well as breast cancer transformation.
• ISK knockout: this model expresses aberrant behavior due to the K+ channel defect, and Waltzer syndrome exhibiting hyperactivity, bi-directional circling, head tilt and bobbing. This has applications to molecular neurobiology, CNS, drug discovery and development.
• HB9 knockout: the minimal promoter for HB9 linked to an exogenous gene to treat neurological diseases and spinal cord injury. This model serves as tools for studying cellular and tissue motor neuron disorders or for use in drug screening.
• ErbB2 conditional knockout: ErbB2 is involved in normal peripheral nervous system development. this model provides a system for the study and treatment for the loss of both motor and sensory neurons.
• YAC128 Huntington disease model: mice expressing human huntingtin protein containing a 128CAG repeat expansion useful for the study of Huntington's disease. Mice develop motor abnormalities, followed by progressive neurodegeneration.

 

These complemetary mouse systems maybe selected for the study of stress/anxiety and drug/alcohol addition, neurodegenerative and neuroendocrine-related disorders.

The mouse strains are fully developed and are available from The Jackson Laboratory.

Third Party Rights

The Howard Hughes Medical Institute and the United States Government provided funding for the development of these animal models.

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Please see downloads for associated academic references.

For licensing inquiries: please contact Andrew R.O. Watson, PhD, Licensing Associate, Oregon Health & Science University, phone: (503)494-8309, email: watson@ohsu.edu.

For shipping inquiries: please contact Peter Wells at The Jackson laboratory http://jaxmice.jax.org/orders/index.html, phone: (207)288-6883, email: peter.wells@jax.org. Price for bundle does not include shipping costs + tax.

The West Coast licensing Partnership (WCLP) is a cooperative network of leading North American research institutions providing a one-stop shop for access to complementary proprietary technologies and research tools. Licensees can select various combinations or "bundles" of unique technologies for drug discovery and/or R&D purposes and obtain non-exclusive rights to their selection of technologies in a single license.

By combining technologies in these areas as a bundle, the WCLP gives access and rights to an increasing number of inventions from a choice of leading institutions.