Peptides related by a C-terminal FLRFamide affect behavior, including panic attack and anxiety. Thus, perturbations in FLRF amide peptide signaling may lead to abnormal mental activity. Although FLRFamide peptides play a role in mental health, their sites of synthesis, regulation of expression and transduction mechanisms are not known. Numerous FLRFamide peptides have been isolated, however no FLRFamide peptide and gene has been identified from a genetically tractable mammal. Thus, the proposed goal is to isolate mouse FLRFamide and delineate its role in mammalian physiology. The proposed hypothesis is that an FLRFamide peptide exists in mouse, a human model system amenable to molecular genetics research, and that the peptide plays a critical role in behaviors. The proposed hypothesis is supported by the following: 1) isolate a mouse FLRFamide peptide, 2) the presence of FLRFamide immunoactivity in mammalian brain, and 3) the structural and functional homology between vertebrate and invertebrate peptides. The principal investigator will test the hypothesis with the following aims: 1) isolate a mouse FLRFamide peptide, 2) clone the mouse FLRFamide cDNA and gene, and 3) determine the distribution of the moue FLRFamide peptide. The investigator will achieve these aims by: 1) purifying an FLRFamide immunoreactive material from a mouse brain homogenate, 2) amplifying the FLRFamide transcript from mouse brain mRNA and screening a mouse genomic library, and 3) raising antisera to the mouse FLRFamide peptide. Accomplishing these aims is crucial to the foundation of the interdisciplinary study to decipher the role of FLRFamide in human physiology. The future research will utilize the power of a molecular genetics approach to generate knockouts and transgenic mice, establish bioassays, and isolate interactive molecules to confirm function, elucidate regulation of expression, and delineate signaling. The proposed research provides the basis of the future design of FLRFamide agonists and antagonists, and assays for mass screening of pharmacological compounds and clinical tests relevant to human health.

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Small Research Grants (R03)
Project #
1R03MH062177-01
Application #
6197944
Study Section
Biochemistry Study Section (BIO)
Program Officer
Asanuma, Chiiko
Project Start
2000-08-01
Project End
2002-07-31
Budget Start
2000-08-01
Budget End
2001-07-31
Support Year
1
Fiscal Year
2000
Total Cost
$75,729
Indirect Cost
Name
University of Michigan Ann Arbor
Department
Biochemistry
Type
Schools of Medicine
DUNS #
791277940
City
Ann Arbor
State
MI
Country
United States
Zip Code
48109