title: Rat transgenic models with a phenotype of intracellular Abeta accumulation in hippocampus and cortex.
abstract: In this communication we report the characterization of several transgenic rat lines expressing human AbetaPP carrying the Swedish and Indiana mutations (coded UKUR28), the human presenilin 1 transgene with the 'Finn' mutation (coded UKUR19) and double transgenic rats expressing both transgenes (coded UKUR25). In these Tg rats, the AbetaPP and PS1 transgene expression was largely restricted to the hippocampus and neocortex. The PS1 transgenic rats did not produce visible changes in Abeta immunoreactivity. The AbetaPP transgenic rats (both the single Tg UKUR28, and double Tg UKUR25) generated a phenotype of intra-neuronalbeta accumulation without plaque formation and with no increased immunoreactivity for AbetaPP amino and carboxyl-terminal epitopes. This phenotype was apparent as early as 6 months of age in the transgenic rat lines carrying the human AbetaPP transgene. No senile plaques of aggregated Abeta were observed in any of the transgenic lines generated, up to 24 months of age. The hAbetaPP single homozygous Tg line (UKUR28) showed an increase in ERK2, without changes in glycogen synthase kinase 3 (GSK3) activity. A preliminary protein analysis of the hippocampus of the double transgenic rat (UKUR25) by mass spectrometry showed differences in the protein profile between this transgenic line and controls.
authors.affiliation: Department of Pharmacology & Therapeutics, McGill University, Montreal, Canada.
authors.forename: Valentina
authors.initials: V
authors.lastname: Echeverria
authors.forename: Adriana
authors.initials: A
authors.lastname: Ducatenzeiler
authors.forename: Leena
authors.initials: L
authors.lastname: Alhonen
authors.forename: Juhani
authors.initials: J
authors.lastname: Janne
authors.forename: Susan M
authors.initials: SM
authors.lastname: Grant
authors.forename: Francisco
authors.initials: F
authors.lastname: Wandosell
authors.forename: Andres
authors.initials: A
authors.lastname: Muro
authors.forename: Francisco
authors.initials: F
authors.lastname: Baralle
authors.forename: Hongshan
authors.initials: H
authors.lastname: Li
authors.forename: Karen
authors.initials: K
authors.lastname: Duff
authors.forename: Moshe
authors.initials: M
authors.lastname: Szyf
authors.forename: A Claudio
authors.initials: AC
authors.lastname: Cuello
mesh_terms: D000544:Alzheimer Disease / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D016564:Amyloid beta-Protein Precursor / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D000818:Animals; D030801:Animals, Genetically Modified; D000911:Antibodies, Monoclonal / Q000276:immunology; D002540:Cerebral Cortex / Q000378:metabolism*; D017931:DNA Primers / Q000235:genetics; D018076:DNA, Complementary / Q000235:genetics; D004195:Disease Models, Animal; D006624:Hippocampus / Q000378:metabolism*; D007150:Immunohistochemistry; D013058:Mass Spectrometry / Q000379:methods; D019950:Mitogen-Activated Protein Kinase 1 / Q000235:genetics; D010641:Phenotype; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D017479:Receptors, Platelet-Derived Growth Factor / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D016564:Amyloid beta-Protein Precursor; D000911:Antibodies, Monoclonal; D017931:DNA Primers; D018076:DNA, Complementary; D012333:RNA, Messenger; D017479:Receptors, Platelet-Derived Growth Factor; D019950:Mitogen-Activated Protein Kinase 1