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, Bernardino Ghetti, J. M. Palacios, L. C. Triarhou

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

Fingerprint

Neurologic Mutant Mice
Amyloid beta-Protein Precursor
In Situ Hybridization
Protein Isoforms
RNA
Cerebellum
Purkinje Cells
Brain
Substantia Nigra
Heterozygote
Mesencephalon
Genes
Neurons
Chromosomes, Human, Pair 16
Cerebellar Cortex
Dopaminergic Neurons
Homozygote
Hippocampus
Gene Expression
Messenger RNA

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

Cite this

@article{4ac8abbf9f75426980b148e2ccd2c704,
title = "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",
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.",
keywords = "Amyloid β-protein precursor, Cerebellum, Gene expression, Mouse chromosome 16, Neurological mutant mouse, Substantia nigra, Weaver",
author = "C. Sola and G. Mengod and Bernardino Ghetti and Palacios, {J. M.} and Triarhou, {L. C.}",
year = "1993",
doi = "10.1016/0169-328X(93)90020-P",
language = "English",
volume = "17",
pages = "340--346",
journal = "Brain Research",
issn = "0006-8993",
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T1 - 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

AU - Sola, C.

AU - Mengod, G.

AU - Ghetti, Bernardino

AU - Palacios, J. M.

AU - Triarhou, L. C.

PY - 1993

Y1 - 1993

N2 - 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.

AB - 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.

KW - Amyloid β-protein precursor

KW - Cerebellum

KW - Gene expression

KW - Mouse chromosome 16

KW - Neurological mutant mouse

KW - Substantia nigra

KW - Weaver

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U2 - 10.1016/0169-328X(93)90020-P

DO - 10.1016/0169-328X(93)90020-P

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