2023
Targeted and selective knockout of the TLQP-21 neuropeptide unmasks its unique role in energy homeostasis
Sahu B, Razzoli M, McGonigle S, Pallais J, Nguyen M, Sadahiro M, Jiang C, Lin W, Kelley K, Rodriguez P, Mansk R, Cero C, Caviola G, Palanza P, Rao L, Beetch M, Alejandro E, Sham Y, Frontini A, Salton S, Bartolomucci A. Targeted and selective knockout of the TLQP-21 neuropeptide unmasks its unique role in energy homeostasis. Molecular Metabolism 2023, 76: 101781. PMID: 37482186, PMCID: PMC10400922, DOI: 10.1016/j.molmet.2023.101781.Peer-Reviewed Original ResearchConceptsGenetic engineering approachesUnique metabolic phenotypeMass spectrometry identificationPrecursor geneGel digestionGenetic lossTLQP-21Cleavage siteC-terminal arginineGenesMutant sequencesSelective knockoutEssential roleBiological constraintsMetabolic phenotypeMouse linesEnergy homeostasisComposite phenotypeMutant miceValuable resourceVGF gene
2020
VGF-derived peptide TLQP-21 modulates microglial function through C3aR1 signaling pathways and reduces neuropathology in 5xFAD mice
El Gaamouch F, Audrain M, Lin WJ, Beckmann N, Jiang C, Hariharan S, Heeger PS, Schadt EE, Gandy S, Ehrlich ME, Salton SR. VGF-derived peptide TLQP-21 modulates microglial function through C3aR1 signaling pathways and reduces neuropathology in 5xFAD mice. Molecular Neurodegeneration 2020, 15: 4. PMID: 31924226, PMCID: PMC6954537, DOI: 10.1186/s13024-020-0357-x.Peer-Reviewed Original ResearchConceptsPeptide TLQP-21TLQP-21BV2 microglial cellsClinical Dementia RatingMicroglial functionAlzheimer's diseasePrimary microgliaMicroglial cellsMurine microgliaSuper agonistMurine BV2 microglial cellsAmyloid plaque densityWild-type microgliaAD-related neuropathologyAccelerating Medicines PartnershipMicroglial cell lineImplanted osmotic pumpsVGF levelsDystrophic neuritesBraak scoresHuman microgliaPlaque densityAD progressionMicroglial genesAmyloid plaques
2016
Embryonic ablation of neuronal VGF increases energy expenditure and reduces body weight
Jiang C, Lin WJ, Sadahiro M, Shin AC, Buettner C, Salton SR. Embryonic ablation of neuronal VGF increases energy expenditure and reduces body weight. Neuropeptides 2016, 64: 75-83. PMID: 28024880, PMCID: PMC5478485, DOI: 10.1016/j.npep.2016.12.005.Peer-Reviewed Original ResearchConceptsVGF knockout miceKnockout miceBody weightPeripheral endocrineEnergy expenditureAdult miceVGF-derived peptide TLQP-21Peptide TLQP-21Diet-induced obesityEmbryonic CNS neuronsICV deliverySynapsin-CreAAV-CreTLQP-21Arcuate nucleusCNS neuronsVentromedial hypothalamusReduced adiposityFemale miceMale miceEmbryonic ablationAdult neuronsExcitatory neuronsHypermetabolic phenotypeEmbryonic neurons
2014
The granin VGF promotes genesis of secretory vesicles, and regulates circulating catecholamine levels and blood pressure
Fargali S, Garcia AL, Sadahiro M, Jiang C, Janssen WG, Lin W, Cogliani V, Elste A, Mortillo S, Cero C, Veitenheimer B, Graiani G, Pasinetti GM, Mahata SK, Osborn JW, Huntley GW, Phillips GR, Benson DL, Bartolomucci A, Salton SR. The granin VGF promotes genesis of secretory vesicles, and regulates circulating catecholamine levels and blood pressure. The FASEB Journal 2014, 28: 2120-2133. PMID: 24497580, PMCID: PMC3986843, DOI: 10.1096/fj.13-239509.Peer-Reviewed Original ResearchConceptsBlood pressureCatecholamine levelsLarge dense-core vesiclesTLQP-21Peptide TLQP-21VGF knockout miceSystolic blood pressureNoradrenergic chromaffin cellsMouse adrenal medullaDense-core vesiclesChronic administrationPlasma epinephrineNeurochemical changesAdrenal norepinephrineEpinephrine contentAdrenal medullaChromaffin cellsCore vesiclesGranin proteinsVGFSignificant increaseMiceSecretionSecretion of proteinsHypertension