Cloning of the Presenilin 2 cDNA and Its Distribution in Brain of the Primate,Microcebus murinus: Coexpression with βAPP and Tau Proteins

A 1340-bp cDNA fragment encoding the lemurian presenilin 2 protein (PS2) was isolated from a Microcebus murinus brain cDNA library by PCR using oligonucleotide primers based on the nucleotide sequence of the human gene. Analysis of five isolated clones showed that the sequence encoded a 448-amino-acid open reading frame, 95.5% identical to the human and 93.5% identical to the mouse presenilin 2 sequences. However, neither the localization of the 2 positions in PS2 nor that of the 43 positions in PS1 associated with early onset Alzheimer's disease were changed. Expression of the presenilin 2 was detected by RT-PCR and compared with that of presenilin 1 and betaAPP in the brain and in peripheral tissues (liver, kidney, and spleen). Immunohistochemistry with a specific polyclonal antiserum raised against a synthetic peptide from the N-terminal part of the human PS2 showed that the protein is distributed throughout the microcebe brain, in vascular and nerve structures. In cortical and in subcortical areas, PS2 labeling was weak and granular in appearance and was scattered throughout the cytoplasm of many neurones, extending into neurites. The gene expression of PS2 increased with age but was not affected by the presence of numerous amyloid plaques. Double labeling immunocytochemistry detected very few neurones with combined immunoreactivity PS2 and APP, or PS2 and Tau.

[1]  D. Albe-Fessard,et al.  A stereotaxic atlas of the grey lesser mouse lemur brain (Microcebus murinus) , 1998, Brain Research Bulletin.

[2]  M. Mattson,et al.  Alzheimer’s Presenilin Mutation Sensitizes Neural Cells to Apoptosis Induced by Trophic Factor Withdrawal and Amyloid β-Peptide: Involvement of Calcium and Oxyradicals , 1997, The Journal of Neuroscience.

[3]  A. Imperato,et al.  Immunohistochemical analysis of presenilin 2 expression in the mouse brain: distribution pattern and co-localization with presenilin 1 protein , 1997, Brain Research.

[4]  D. Walker,et al.  Expression of presenilin-1 and -2 mRNAs in rat and Alzheimer's disease brains , 1997, Brain Research.

[5]  P. Hof,et al.  Presenilin-1-immunoreactive neurons are preserved in late-onset Alzheimer's disease. , 1997, The American journal of pathology.

[6]  Christopher C. J. Miller,et al.  Tau phosphorylation in cells transfected with wild-type or an Alzheimer's disease mutant Presenilin 1 , 1997, Neuroscience Letters.

[7]  B. Hyman,et al.  Developmental Regulation of Presenilin mRNA Expression Parallels Notch Expression , 1997, Journal of neuropathology and experimental neurology.

[8]  T. Sunderland,et al.  Participation of Presenilin 2 in Apoptosis: Enhanced Basal Activity Conferred by an Alzheimer Mutation , 1996, Science.

[9]  L. Forno,et al.  Antibodies to presenilin proteins detect neurofibrillary tangles in Alzheimer's disease. , 1996, The American journal of pathology.

[10]  D. Price,et al.  Expression of Presenilin 1 and 2 (PS1 and PS2) in Human and Murine Tissues , 1996, The Journal of Neuroscience.

[11]  B. Hyman,et al.  In situ hybridization analysis of presenilin 1 mRNA in Alzheimer disease and in lesioned rat brain. , 1996, Proceedings of the National Academy of Sciences of the United States of America.

[12]  A. Calenda,et al.  Molecular cloning, sequencing, and brain expression of the presenilin 1 gene in Microcebus murinus. , 1996, Biochemical and biophysical research communications.

[13]  C. Cotman,et al.  Alzheimer‐associated presenilin‐2 confers increased sensitivity to poptosis in PC12 cells , 1996, FEBS letters.

[14]  D. Selkoe,et al.  The Alzheimer’s Disease-Associated Presenilins Are Differentially Phosphorylated Proteins Located Predominantly within the Endoplasmic Reticulum , 1996, Molecular medicine.

[15]  D. Dorsa,et al.  Neuronal expression of STM2 mRNA in human brain is reduced in Alzheimer's disease. , 1996, The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society.

[16]  Kenneth S. Kosik,et al.  The E280A presenilin 1 Alzheimer mutation produces increased Aβ42 deposition and severe cerebellar pathology , 1996, Nature Medicine.

[17]  C. Cotman,et al.  Gene expression of Alzheimer‐associated presenilin‐2 in the frontal cortex of Alzheimer and aged control brain , 1996, FEBS letters.

[18]  C. Duyckaerts,et al.  Widespread immunoreactivity of presenilin in neurons of normal and Alzheimer’s disease brains: double-labeling immunohistochemical study , 1996, Acta Neuropathologica.

[19]  Y. Agid,et al.  Regional and cellular presenilin 2 (STM2) gene expression in the human brain. , 1996, Neuroreport.

[20]  G. Schellenberg,et al.  Secreted amyloid β–protein similar to that in the senile plaques of Alzheimer's disease is increased in vivo by the presenilin 1 and 2 and APP mutations linked to familial Alzheimer's disease , 1996, Nature Medicine.

[21]  A. Calenda,et al.  β-Amyloid Protein Precursor inMicrocebus murinus:Genotyping and Brain Localization , 1996, Neurobiology of Disease.

[22]  G. Schellenberg,et al.  Genomic structure and expression of STM2, the chromosome 1 familial Alzheimer disease gene. , 1996, Genomics.

[23]  B. Hyman,et al.  Alzheimer–associated presenilins 1 and 2 : Neuronal expression in brain and localization to intracellular membranes in mammalian cells , 1996, Nature Medicine.

[24]  D. Selkoe,et al.  Identification of amyloid beta protein in the brain of the small, short-lived Lemurian primate Microcebus murinus , 1994, Neurobiology of Aging.

[25]  N. Bons,et al.  Senile plaques and neurofibrillary changes in the brain of an aged lemurian primate, Microcebus murinus , 1992, Neurobiology of Aging.

[26]  C. van Broeckhoven,et al.  Presenilin mutations in Alzheimer's disease , 1998, Human mutation.

[27]  A. Delacourte,et al.  Immunocytochemical characterization of Tau proteins during cerebral aging of the lemurian primate Microcebus murinus. , 1995, Comptes rendus de l'Academie des sciences. Serie III, Sciences de la vie.