Regional distribution of the alternatively spliced isoforms of βAPP RNA transcript in the brain of normal, heterozygous and homozygous weaver mutant mice as revealed by in situ hybridization histochemistry

C. Sola, G. Mengod, B. Ghetti, J. M. Palacios, L. C. Triarhou

Research output: Contribution to journalArticle

8 Scopus citations

Abstract

The cellular localization of amyloid β-protein precursor (βAPP) RNA transcripts was studied by in situ hybridization histochemistry in normal, heterozygous and homozygous weaver (wv) mutant mice, which lose midbrain dopamine (DA neurons, cerebrall granule cells, and Purkinje cells. The βAPP gene is located at the distal end of mouse chromosome (MMU) 16, on which the wv locus has been assigned as well. Transcripts encoding isoforms βAPP695, βAPP714 and βAPP751 were present in several different brain areas of normal (+/+) mice,including hippocampus, substantia nigra (SN) pars compacta and cerebellum. The same transcripts were progressively reduced in homozygous weaver (wv/wv) SN, in correlation with DA neuron loss. The βAPP770 species - normally seen in striatum and not SN - was present in the mutant striatum. There were not any obvious changes in βAPP expression in the nigrostriatal system of weaver heterozygotes (wv/+). In normal cerebellum, Purkinje cells showed very high levels of hybridization signal for βAPP695, βAPP714 and βAPP751 RNA transcripts, and a moderate signal for the βAPP770 species. In weaver heterozygotes and homozygotes, Purkinje cells, which are typically not arranged in a monolayer, showed strong hybridization signal. No changes in βAPP mRNAs were observed in brain areas other than the cerebellum and ventral midbrain of weaver mutants. These findings suggest that the decreased βAPP gene expression seen in the cerebellum and SN of weaver mutants most likely represents an epiphenomenon of the regional nerve cell loss and, therefore, the wv gene defect on MMU 16 does not seem to influence the expression of the closely linked βAPP gene in brain areas outside the nigrostriatal pathway and cerebellar cortex.

Original languageEnglish (US)
Pages (from-to)340-346
Number of pages7
JournalMolecular Brain Research
Volume17
Issue number3-4
DOIs
StatePublished - Mar 1993

Keywords

  • Amyloid β-protein precursor
  • Cerebellum
  • Gene expression
  • Mouse chromosome 16
  • Neurological mutant mouse
  • Substantia nigra
  • Weaver

ASJC Scopus subject areas

  • Molecular Biology
  • Cellular and Molecular Neuroscience

Fingerprint Dive into the research topics of 'Regional distribution of the alternatively spliced isoforms of βAPP RNA transcript in the brain of normal, heterozygous and homozygous weaver mutant mice as revealed by in situ hybridization histochemistry'. Together they form a unique fingerprint.

  • Cite this