Serotonin-Deficient Knock-out Mouse

Description of Invention:
Serotonin is an important modulator of many developmental, behavioral, and physiological processes, and it has been implicated in depression, anxiety, schizophrenia, obsessive compulsive disorders, and substance abuse. Serotonin’s pharmacology is extremely complex and it is mediated by seven of serotonin receptor subtypes and it is present in several tissues. Although it has been a subject of a number of studies, its role has been difficult to ascertain. To investigate the role of serotonin in these disorders, the murine gene was disrupted by homologous recombination. Results indicate that serotonin binding sites were absent in different brain regions (brain stem, frontal cortex, hippocampus, and striatum), and its concentrations were reduced by 60-80%. These mice represent a powerful tool for the investigation of behavioral and neuropsychiatric disorders, and development of drug treatments for these disorders.

Applications:
A model to study serotonin’s role in behavioral and neuropsychiatric disorders.

Inventors:
Dennis L Murphy (NIMH)


Patent Status:
Research Tool -- patent protection is not being pursued for this technology

Relevant Publication:

1. RF Ren-Patterson, LW Cochran, A Holmes, S Sherrill, SJ Huang, T Tolliver, K-P Lesch. Loss of brain-derived neurotrophic factor gene allele exacerbates brain monoamine deficiencies and increases stress abnormalities of serotonin transporter knockout mice. J Neurosci Res. 2005 Mar 15:79(6):756-771. [ PubMed abs ]
2. DL Murphy, A Lerner, G Rudnick, K-P Lesch. Serotonin transporter: gene, genetic disorders, and pharmacogenetics. Mol Interv. 2004 April:4(2):109-123. [ PubMed abs ]
3. RF Ren-Patterson, D-K Kim, X Zheng, S Sherrill, S-J Huang, T Tolliver, DL Murphy. Serotonergic-like progenitor cells propagated from neural stem cells in vitro: survival with SERT protein expression following implantation into brains of mice lacking SERT. FASEB J. 2005 Sep:19(11):1537-1539. [ PubMed abs ]
4. Q Li, A Holmes, L Ma, LD Van de Kar, F Garcia, DL Murphy. Medial hypothalamic 5-hydroxytryptamine (5HT)1A receptors regulate neuroendocrine responses to stress and exploratory locomotor activity application of recombinant adenovirus containing 5-HT1A sequences. J Neurosci. 2004 Dec 1:24(48):10868-10877. [ PubMed abs ]
5. F Kilic, DL Murphy, G Rudnick. A human serotonin transporter mutation causes constitutive activation of transport activity. Mol Pharmacol. 2003 Aug:64(2):440-446. [ PubMed abs ]
6. DL Murphy, GR Uhl, A Holmes, R Ren-Patterson, FS Hall, I Sora, S Detera-Wadleigh, K-P Lesch. Experimental gene interaction studies with SERT mutant mice as models for human polygenic and epistatic traits and disorders. Genes Brain Behav. 2003 Dec:2(6):350-364. [ PubMed abs ]
7. N Ozaki, D Goldman, WH Kaye, K Plotnicov, BD Greenberg, J Lappalainen, G Rudnick, DL Murphy. Serotonin transporter missense mutation associated with a complex neuropsychiatric phenotype. Mol Psychiatry. 2003 Nov:8(11):933-936. [ PubMed abs ]

Licensing Status:
This technology is available as a research tool under a Biological Materials License.


Portfolios:
Devices/Instrumentation
Devices/Instrumentation - Research Tools and Materials
Miscellaneous
Central Nervous System
Central Nervous System - Research Materials



For Additional Information Please Contact:
Jennifer Wong
NIH Office of Technology Transfer
6011 Executive Blvd. Suite 325,
Rockville, MD 20852
United States
Email: wongje@mail.nih.gov
Phone: 301-435-4633
Fax: 301-402-0220


Ref No: 1514

Updated: 03/2007