Cellular distribution of the RNA transcripts of a newly discovered gene in the brain of normal, weaver, Purkinje cell degeneration and reeler mutant mice as evidenced by in situ hybridization histochemistry

M. Kambouris, L. Sangameswaran, S. R. Dlouhy, M. E. Hodes, B. Ghetti, L. C. Triarhou

Research output: Contribution to journalArticlepeer-review

4 Scopus citations

Abstract

After we identified several novel cDNAs by screening a neonatal (P1) heterozygous weaver (wv/+) cerebellar cDNA expression library with a rabbit anti-mouse granule cell antiserum, we characterized and sequenced one cDNA, GCAP-8 (standing for granule cell antiserum positive, clone number 8). In this study we examined its expression and cellular distribution in adult cerebellar mutant mice as evidenced by in situ hybridization histochemistry. In wild-type (+/+) brain, strong hybridization signal is seen in cerebellum, hippocampus, substantia nigra (SN), and cerebral cortex; in the cerebellum, hybridization signal is seen in granule cells, Purkinje cells, and in cells of the deep cerebellar nuclei. In the granuloprival weaver (wv / wv) cerebellum, hybridization signal is seen mainly in Purkinje cells. GCAP-8 expression is reduced in wv / wv SN pars compacta, which is known to lose dopamine (DA) neurons. In Purkinje cell degeneration (pcd / pcd) mutants, granule cells show hybridization signal, but overall expression is decreased owing to the absence of Purkinje cells. In reeler (rl / rl) cerebellum, the strongest hybridization signal is found in a thin granule cell layer without the typical foliation pattern, while grain clusters representing ectopic Purkinje cells are observed in the subcortical white matter and the area of the deep cerebellar nuclei. GCAP-8 expression in the reeler hippocampus and cerebral cortex shows a mixing of layers, which is known to be an aspect of the histological phenotype of this mutant. These results indicate that (i) GCAP-8 is expressed by multiple neuronal populations, both synaptically connected and anatomically unrelated to each other, (ii) expression of GCAP-8 mRNA appears to be intrinsically regulated and not to depend on trans-acting (including transsynaptic) elements produced by other neuronal cell types, and (iii) the mutations studied do not affect the general expression of GCAP-8 in non-affected brain areas. The correlation of the cellular expression of GCAP-8 with the known anatomical deficits in mutants may be useful in studying the intrinsic components of selective neuronal populations, their ontogenetic properties, and pathophysiological mechanisms operating in hereditary ataxias.

Original languageEnglish (US)
Pages (from-to)321-328
Number of pages8
JournalMolecular Brain Research
Volume18
Issue number4
DOIs
StatePublished - Jun 1993

Keywords

  • cDNA
  • Cerebellum
  • Gene expression
  • Hippocampus
  • In situ hybridization
  • Neurological mutant mice
  • Purkinje cell degeneration (pcd)
  • Reeler
  • Substantia nigra
  • Weaver

ASJC Scopus subject areas

  • Molecular Biology
  • Cellular and Molecular Neuroscience

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