Phenotypic knockout of nerve growth factor in adult transgenic mice reveals severe deficits in basal forebrain cholinergic neurons, cell death in the spleen, and skeletal muscle dystrophy

Francesca Ruberti, Simona Capsoni, Alessandro Comparini, Elena Di Daniel, Jessica Franzot, Stefania Gonfloni, Gabriella Rossi, Nicoletta Berardi, Antonino Cattaneo

Research output: Contribution to journalArticle

Abstract

The disruption of the nerve growth factor (NGF) gene in transgenic mice leads to a lethal phenotype (Crowley et al., 1994) and hinders the study of NGF functions in the adult. In this study the phenotypic knockout of NGF in adult mice was achieved by expressing transgenic anti-NGF antibodies, under the control of the human cytomegalovirus promoter. In adult mice, antibody levels are 2000-fold higher than in newborns. Classical NGF targets, including sympathetic and sensory neurons, are severely affected. In the CNS, basal forebrain and hippocampal cholinergic neurons are not affected in the early postnatal period, whereas they are greatly reduced in the adult (55 and 62% reduction, respectively). Adult mice show a reduced ability in spatial learning behavioral tasks. Adult, but not neonatal, transgenic mice further show a new phenotype at the level of peripheral tissues, such as apoptosis in the spleen and dystrophy of skeletal muscles. The analysis of this novel comprehensive transgenic model settles the controversial issue regarding the NGF dependence of cholinergic neurons in adult animals and reveals new NGF functions in adult non-neuronal tissues. The results demonstrate that the decreased availability of NGF in the adult causes phenotypic effects via processes that are at least partially distinct from early developmental effects of NGF deprivation.

Original languageEnglish
Pages (from-to)2589-2601
Number of pages13
JournalJournal of Neuroscience
Volume20
Issue number7
Publication statusPublished - Apr 1 2000

Keywords

  • Adult transgenic mice
  • Apoptosis
  • Behavioral impairment
  • Cholinergic deficits
  • Muscular dystrophy
  • Neurotrophins
  • Spleen

ASJC Scopus subject areas

  • Neuroscience(all)

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    Ruberti, F., Capsoni, S., Comparini, A., Di Daniel, E., Franzot, J., Gonfloni, S., Rossi, G., Berardi, N., & Cattaneo, A. (2000). Phenotypic knockout of nerve growth factor in adult transgenic mice reveals severe deficits in basal forebrain cholinergic neurons, cell death in the spleen, and skeletal muscle dystrophy. Journal of Neuroscience, 20(7), 2589-2601.