Regional distribution of amyloid β-protein precursor, growth-associated phosphoprotein-43 and microtubule-associated protein 2 messenger RNAs in the nigrostriatal system of normal and weaver mutant mice and effects of ventral mesencephalic grafts

C. Sola, G. Mengod, W. C. Low, J. Norton, Bernardino Ghetti, J. M. Palacios, L. C. Triarhou

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Abstract

Using in situ hybridization histochemistry with [32P]oligonucleotide probes, we studied the cellular localization of RNA transcripts for amyloid β-protein precursor (βAPP), growth-associated phosphoprotein-43 (GAP-43) and microtubule-associated protein 2 (MAP2) in the mesostriatal system of normal (+/+) and weaver (wv/wv) mutant mice, which lose mesencephalic dopamine neurons. In addition, expression of the same messages was studied in ventral mesencephalic cell suspensions transplanted to the weaver striatum. Transcripts encoding GAP-43, MAP2 and isoforms βAPP695, βAPP714 and βAPP751 were present in normal substantia nigra and progressively reduced in weaver substantia nigra; such a reduction was correlated with dopamine neuron loss. The survival of dopamine neurons in unilateral intrastriatal grafts was documented by methamphetamine-induced rotational asymmetry tests and by tyrosine hydroxylase immunocytochemistry. High hybridization signals were obtained for GAP-43, MAP2, βAPP695, βAPP714 and βAPP751 RNA transcripts in the grafted tissue; the βAPP770 species-normally seen in striatum and not substantia nigra-was not expressed in the grafts, but it was present in the recipient striatum. Following immunocytochemical labelling with antibodies, GAP-43 and MAP2 immunoreactivities were seen in cell processes in the grafts and surrounding tissue, whereas βAPP immunoreactivity was mainly found in grafted cell bodies. These results suggest that the transplanted mesencephalic cells mature very similarly to those in the normal substantia nigra, expressing different mRNAs that are normally present in the ventral midbrain and which are reduced in the weaver mutant as a consequence of dopamine neuron loss.

Original languageEnglish
Pages (from-to)1442-1454
Number of pages13
JournalEuropean Journal of Neuroscience
Volume5
Issue number11
DOIs
StatePublished - 1993

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Neurologic Mutant Mice
Microtubule-Associated Proteins
Amyloid beta-Protein Precursor
Dopaminergic Neurons
Phosphoproteins
Substantia Nigra
Transplants
Messenger RNA
Growth
RNA
Methamphetamine
Oligonucleotide Probes
Tyrosine 3-Monooxygenase
Mesencephalon
In Situ Hybridization
Suspensions
Protein Isoforms
Immunohistochemistry
Antibodies

Keywords

  • Gene expression
  • Neural transplant
  • Neurological mutant mice
  • Substantia nigra

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

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title = "Regional distribution of amyloid β-protein precursor, growth-associated phosphoprotein-43 and microtubule-associated protein 2 messenger RNAs in the nigrostriatal system of normal and weaver mutant mice and effects of ventral mesencephalic grafts",
abstract = "Using in situ hybridization histochemistry with [32P]oligonucleotide probes, we studied the cellular localization of RNA transcripts for amyloid β-protein precursor (βAPP), growth-associated phosphoprotein-43 (GAP-43) and microtubule-associated protein 2 (MAP2) in the mesostriatal system of normal (+/+) and weaver (wv/wv) mutant mice, which lose mesencephalic dopamine neurons. In addition, expression of the same messages was studied in ventral mesencephalic cell suspensions transplanted to the weaver striatum. Transcripts encoding GAP-43, MAP2 and isoforms βAPP695, βAPP714 and βAPP751 were present in normal substantia nigra and progressively reduced in weaver substantia nigra; such a reduction was correlated with dopamine neuron loss. The survival of dopamine neurons in unilateral intrastriatal grafts was documented by methamphetamine-induced rotational asymmetry tests and by tyrosine hydroxylase immunocytochemistry. High hybridization signals were obtained for GAP-43, MAP2, βAPP695, βAPP714 and βAPP751 RNA transcripts in the grafted tissue; the βAPP770 species-normally seen in striatum and not substantia nigra-was not expressed in the grafts, but it was present in the recipient striatum. Following immunocytochemical labelling with antibodies, GAP-43 and MAP2 immunoreactivities were seen in cell processes in the grafts and surrounding tissue, whereas βAPP immunoreactivity was mainly found in grafted cell bodies. These results suggest that the transplanted mesencephalic cells mature very similarly to those in the normal substantia nigra, expressing different mRNAs that are normally present in the ventral midbrain and which are reduced in the weaver mutant as a consequence of dopamine neuron loss.",
keywords = "Gene expression, Neural transplant, Neurological mutant mice, Substantia nigra",
author = "C. Sola and G. Mengod and Low, {W. C.} and J. Norton and Bernardino Ghetti and Palacios, {J. M.} and Triarhou, {L. C.}",
year = "1993",
doi = "10.1111/j.1460-9568.1993.tb00212.x",
language = "English",
volume = "5",
pages = "1442--1454",
journal = "European Journal of Neuroscience",
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TY - JOUR

T1 - Regional distribution of amyloid β-protein precursor, growth-associated phosphoprotein-43 and microtubule-associated protein 2 messenger RNAs in the nigrostriatal system of normal and weaver mutant mice and effects of ventral mesencephalic grafts

AU - Sola, C.

AU - Mengod, G.

AU - Low, W. C.

AU - Norton, J.

AU - Ghetti, Bernardino

AU - Palacios, J. M.

AU - Triarhou, L. C.

PY - 1993

Y1 - 1993

N2 - Using in situ hybridization histochemistry with [32P]oligonucleotide probes, we studied the cellular localization of RNA transcripts for amyloid β-protein precursor (βAPP), growth-associated phosphoprotein-43 (GAP-43) and microtubule-associated protein 2 (MAP2) in the mesostriatal system of normal (+/+) and weaver (wv/wv) mutant mice, which lose mesencephalic dopamine neurons. In addition, expression of the same messages was studied in ventral mesencephalic cell suspensions transplanted to the weaver striatum. Transcripts encoding GAP-43, MAP2 and isoforms βAPP695, βAPP714 and βAPP751 were present in normal substantia nigra and progressively reduced in weaver substantia nigra; such a reduction was correlated with dopamine neuron loss. The survival of dopamine neurons in unilateral intrastriatal grafts was documented by methamphetamine-induced rotational asymmetry tests and by tyrosine hydroxylase immunocytochemistry. High hybridization signals were obtained for GAP-43, MAP2, βAPP695, βAPP714 and βAPP751 RNA transcripts in the grafted tissue; the βAPP770 species-normally seen in striatum and not substantia nigra-was not expressed in the grafts, but it was present in the recipient striatum. Following immunocytochemical labelling with antibodies, GAP-43 and MAP2 immunoreactivities were seen in cell processes in the grafts and surrounding tissue, whereas βAPP immunoreactivity was mainly found in grafted cell bodies. These results suggest that the transplanted mesencephalic cells mature very similarly to those in the normal substantia nigra, expressing different mRNAs that are normally present in the ventral midbrain and which are reduced in the weaver mutant as a consequence of dopamine neuron loss.

AB - Using in situ hybridization histochemistry with [32P]oligonucleotide probes, we studied the cellular localization of RNA transcripts for amyloid β-protein precursor (βAPP), growth-associated phosphoprotein-43 (GAP-43) and microtubule-associated protein 2 (MAP2) in the mesostriatal system of normal (+/+) and weaver (wv/wv) mutant mice, which lose mesencephalic dopamine neurons. In addition, expression of the same messages was studied in ventral mesencephalic cell suspensions transplanted to the weaver striatum. Transcripts encoding GAP-43, MAP2 and isoforms βAPP695, βAPP714 and βAPP751 were present in normal substantia nigra and progressively reduced in weaver substantia nigra; such a reduction was correlated with dopamine neuron loss. The survival of dopamine neurons in unilateral intrastriatal grafts was documented by methamphetamine-induced rotational asymmetry tests and by tyrosine hydroxylase immunocytochemistry. High hybridization signals were obtained for GAP-43, MAP2, βAPP695, βAPP714 and βAPP751 RNA transcripts in the grafted tissue; the βAPP770 species-normally seen in striatum and not substantia nigra-was not expressed in the grafts, but it was present in the recipient striatum. Following immunocytochemical labelling with antibodies, GAP-43 and MAP2 immunoreactivities were seen in cell processes in the grafts and surrounding tissue, whereas βAPP immunoreactivity was mainly found in grafted cell bodies. These results suggest that the transplanted mesencephalic cells mature very similarly to those in the normal substantia nigra, expressing different mRNAs that are normally present in the ventral midbrain and which are reduced in the weaver mutant as a consequence of dopamine neuron loss.

KW - Gene expression

KW - Neural transplant

KW - Neurological mutant mice

KW - Substantia nigra

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JO - European Journal of Neuroscience

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