Progranulin expression in the developing and adult murine brain

Terri L. Petkau, S. J. Neal, P. C. Orban, J. L. MacDonald, A. M. Hill, G. Lu, H. H. Feldman, I. R.A. MacKenzie, B. R. Leavitt

Research output: Contribution to journalArticle

79 Scopus citations

Abstract

Frontotemporal lobar degeneration (FTLD) is a neurodegenerative condition characterized by focal degeneration of the frontal and temporal lobes of the brain. Autosomal dominantly inherited mutations of the pro- granulin gene (GRN) have been identified as the cause of a subset of cases of familial FTLD. In order to better understand the function of progranulin in the central nervous system (CNS), we have assessed the spatio-temporal expression pattern of both the murine progranulin gene (Grn) and the protein (Grn) by using transgenic knock-in mice expressing a reporter gene from the Grn locus and by immunohistochemistry, respectively. We compared Grn expression with a panel of established markers for distinct neuronal developmental stages and specific cell lineages at time points ranging from embryonic day 13.5 through to the mature adult. We find that Grn is expressed in both neurons and microglia within the CNS, but that it shows a different developmental expression pattern in each cell type. Grn expression in neurons increases as the cells mature, whereas expression in microglia varies with the cells' state of activation, being specifically upregulated in microglia in response to excitotoxic injury. Our results suggest that progranulin plays distinct roles in neurons and microglia, both of which likely contribute to overall neuronal health and function.

Original languageEnglish (US)
Pages (from-to)3931-3947
Number of pages17
JournalJournal of Comparative Neurology
Volume518
Issue number19
DOIs
StatePublished - Oct 1 2010
Externally publishedYes

Keywords

  • Frontotemporal dementia
  • Immunohistochemistry
  • Knockout mouse
  • LacZ reporter

ASJC Scopus subject areas

  • Neuroscience(all)

Fingerprint Dive into the research topics of 'Progranulin expression in the developing and adult murine brain'. Together they form a unique fingerprint.

  • Cite this

    Petkau, T. L., Neal, S. J., Orban, P. C., MacDonald, J. L., Hill, A. M., Lu, G., Feldman, H. H., MacKenzie, I. R. A., & Leavitt, B. R. (2010). Progranulin expression in the developing and adult murine brain. Journal of Comparative Neurology, 518(19), 3931-3947. https://doi.org/10.1002/cne.22430