title: A transgenic marker for newly born granule cells in dentate gyrus.
abstract: Neurogenesis in the dentate gyrus continues into adulthood, yet little is known about the function of newly born neurons or how they integrate into an existing network of mature neurons. We made transgenic mice that selectively and transiently express enhanced green fluorescent protein (EGFP) in newly born granule cells of the dentate gyrus under the transcriptional control of proopiomelanocortin (POMC) genomic sequences. Analysis of transgenic pedigrees with truncation or deletion mutations indicated that EGFP expression in the dentate gyrus required cryptic POMC promoter regions dispensable for arcuate hypothalamic or pituitary expression. Unlike arcuate neurons, dentate granule cells did not express the endogenous POMC gene. EGFP-positive neurons had immature properties, including short spineless dendrites and small action potentials. Colocalization with bromodeoxyuridine indicated that EGFP-labeled granule cells were approximately 2 weeks postmitotic. EGFP-labeled cells expressed markers for immature granule cells but not the glial marker GFAP. The number of EGFP-labeled neurons declined with age and increased with exercise, paralleling neurogenesis. Our results indicate that POMC-EGFP marks immature granule cells and that adult-generated granule cells integrate quite slowly into the hippocampal circuitry.
authors.affiliation: Vollum Institute, Oregon Health and Science University, Portland, Oregon 97239, USA. overstre@ohsu.edu
authors.forename: Linda S
authors.initials: LS
authors.lastname: Overstreet
authors.forename: Shane T
authors.initials: ST
authors.lastname: Hentges
authors.forename: Viviana F
authors.initials: VF
authors.lastname: Bumaschny
authors.forename: Flavio S J
authors.initials: FS
authors.lastname: de Souza
authors.forename: James L
authors.initials: JL
authors.lastname: Smart
authors.forename: Andrea M
authors.initials: AM
authors.lastname: Santangelo
authors.forename: Malcolm J
authors.initials: MJ
authors.lastname: Low
authors.forename: Gary L
authors.initials: GL
authors.lastname: Westbrook
authors.forename: Marcelo
authors.initials: M
authors.lastname: Rubinstein
mesh_terms: D000200:Action Potentials / Q000502:physiology; D000375:Aging / Q000378:metabolism; D000818:Animals; D015415:Biomarkers / Q000032:analysis; D001973:Bromodeoxyuridine; D002452:Cell Count; D002455:Cell Division / Q000502:physiology; D002465:Cell Movement; D018891:Dentate Gyrus / Q000166:cytology / Q000378:metabolism*; D017930:Genes, Reporter; D049452:Green Fluorescent Proteins; D008164:Luminescent Proteins / Q000096:biosynthesis / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D039842:Neural Cell Adhesion Molecule L1 / Q000096:biosynthesis; D009474:Neurons / Q000378:metabolism*; D005082:Physical Exertion / Q000502:physiology; D011333:Pro-Opiomelanocortin / Q000235:genetics; D011401:Promoter Regions, Genetic / Q000502:physiology; D012794:Sialic Acids / Q000096:biosynthesis; D019076:Transgenes / Q000502:physiology*
chemical_list: D015415:Biomarkers; D008164:Luminescent Proteins; D039842:Neural Cell Adhesion Molecule L1; D012794:Sialic Acids; C103469:polysialyl neural cell adhesion molecule; D049452:Green Fluorescent Proteins; D011333:Pro-Opiomelanocortin; D001973:Bromodeoxyuridine