A transgenic rat expressing human APP with the Swedish Alzheimer’s disease mutation

Folkesson, Ronnie; Małkiewicz, Katarzyna; Kloskowska, Ewa; Nilsson, Tony; Popova, Elena; Bogdanović, Nenad; Ganten, Ursula; Ganten, Detlev; Bäder, Michael; Winblad, Bengt; Benedikz, Eiríkur

doi:10.1016/j.bbrc.2007.04.195

Cited by 36 publications

(30 citation statements)

References 21 publications

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“…Yet despite the lack of a plaque and tangle pathology presenilin FAD mutant mice exhibit a wide range of anatomic, electrophysiological and biochemical changes that mimic many of the features of AD (Elder et al 2010b). Rat models while becoming more available appear to suVer the same limitations as models in the mouse requiring high-level expression of an APP FAD mutation to induce signiWcant plaque pathology (Table 1; Bugos et al 2009;Clarke et al 2007;Echeverria et al 2004;Agca et al 2008;Flood et al 2009;Folkesson et al 2007;Leon et al 2010;Liu et al 2008a;Ruiz-Opazo et al 2004). …”

Section: Knock-in Mutant Htt Using Homologous Recombination In Es Cellsmentioning

confidence: 95%

“…Presence of nuclear staining and microaggregates early in the course of the disease. Early overt behavioral changes seen and strength of the phenotype generally correlated with the number of CAG repeats (-200) (Heng et al 2009;Levine et al 2004;Lin et al 2001;Raymond et al 2011;Shelbourne et al 1999;Wheeler et al 2000;White et al 1997 (Bugos et al 2009;Clarke et al 2007;Echeverria et al 2004;Agca et al 2008;Flood et al 2009;Folkesson et al 2007;Liu et al 2008a;Ruiz-Opazo et al 2004 of A 3-42 after cleavage (Link 1995). Expression of this human A 42 minigene in muscle cells resulted in progressive paralysis and staining of muscle cells with a human A 42 speciWc antibody revealed A 42 deposits that reacted with Congo red and thioXavin S. Ultrastructural studies, however, revealed that the deposits were intracytoplasmic rather than extracellular as are amyloid plaques found in AD (Ewald and Li 2010).…”

Section: Knock-in Mutant Htt Using Homologous Recombination In Es Cellsmentioning

confidence: 98%

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Modeling human neurodegenerative diseases in transgenic systems

2011

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Transgenic systems are widely used to study the cellular and molecular basis of human neurodegenerative diseases. A wide variety of model organisms have been utilized, including bacteria (Escherichia coli), plants (Arabidopsis thaliana), nematodes (Caenorhabditis elegans), arthropods (Drosophila melanogaster), fish (zebrafish, Danio rerio), rodents (mouse, Mus musculus and rat, Rattus norvegicus) as well as non-human primates (rhesus monkey, Macaca mulatta). These transgenic systems have enormous value for understanding the pathophysiological basis of these disorders and have, in some cases, been instrumental in the development of therapeutic approaches to treat these conditions. In this review, we discuss the most commonly used model organisms and the methodologies available for the preparation of transgenic organisms. Moreover, we provide selected examples of the use of these technologies for the preparation of transgenic animal models of neurodegenerative diseases, including Alzheimer's disease (AD), frontotemporal lobar degeneration (FTLD), amyotrophic lateral sclerosis (ALS), Huntington's disease (HD) and Parkinson's disease (PD) and discuss the application of these technologies to AD as an example of how transgenic modeling has affected the study of human neurodegenerative diseases.

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Section: Knock-in Mutant Htt Using Homologous Recombination In Es Cellsmentioning

confidence: 95%

Section: Knock-in Mutant Htt Using Homologous Recombination In Es Cellsmentioning

confidence: 98%

Modeling human neurodegenerative diseases in transgenic systems

2011

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“…Thus far, there is only one exception in which AD-related genetic manipulations have been performed in the rat [159] , whereas the majority of lesion studies have been performed using rats. This difference raises the question of whether results from lesion studies in rats can be generalized to mice, but this seems highly likely as it is already accepted that information from rat studies are informative as to the basic neurobiology of learning and memory, including that found in humans.…”

Section: Transgenic and Lesion Models Are Complementary: Let's Combinmentioning

confidence: 99%

Coexisting Cholinergic and Parahippocampal Degeneration: A Key to Memory Loss in Dementia and a Challenge for Transgenic Models?

et al. 2008

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One century after Alzheimer’s initial report, a variety of animal models of Alzheimer’s disease (AD) are being used to mimic one or more pathological signs viewed as critical for the evolution of cognitive decline in dementia. Among the most common are, (a) traditional lesion models aimed at reproducing the degeneration of one of two key brain regions affected in AD, namely the cholinergic basal forebrain (CBF) and the transentorhinal region, and (b) transgenic mouse models aimed at reproducing AD histopathological hallmarks, namely amyloid plaques and neurofibrillary tangles. These models have provided valuable insights into the development and consequences of the pathology, but they have not consistently reproduced the severity of memory deficits exhibited in AD. The reasons for this lack of correspondence with the severity of expected deficits may include the limited replication of multiple neuropathology in potentially key brain regions. A recent lesion model in the rat found that severe memory impairment was obtained only when the two traditional lesions were combined together (i.e. conjoint CBF and entorhinal cortex lesions), indicative of a dramatic impact on cognitive function when there is coexisting, rather than isolated, damage in these two brain regions. It is proposed that combining AD transgenic mouse models with additional experimental damage to both the CBF and entorhinal regions might provide a unique opportunity to further understand the evolution of the disease and improve treatments of severe cognitive dysfunction in neurodegenerative dementias.

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“…To date, several transgenic rat strains have been generated to model familial Alzheimer's disease (Echeverria et al 2004;Ruiz-Opazo et al 2004;Flood et al 2007;Folkesson et al 2007;Agca et al 2008), human tauopathies (Zilka et al 2006), Huntington's disease (von Hörsten et al 2003), or amyotrophic lateral sclerosis (Nagai et al 2001;Howland et al 2002) (for details see Table 2). …”

Section: The Rat Models For Human Neurodegenerative Disordersmentioning

confidence: 99%

Beyond the Rat Models of Human Neurodegenerative Disorders

2009

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The rat is a model of choice in biomedical research for over a century. Currently, the rat presents the best "functionally" characterized mammalian model system. Despite this fact, the transgenic rats have lagged behind the transgenic mice as an experimental model of human neurodegenerative disorders. The number of transgenic rat models recapitulating key pathological hallmarks of Alzheimer's disease, Huntington's disease, amyotrophic lateral sclerosis, or human tauopathies is still limited. The reason is that the transgenic rats remain more difficult to produce than transgenic mice. The gene targeting technology is not yet established in rats due to the lack of truly totipotent embryonic stem cells and cloning technology. This extremely powerful technique has given the mouse a clear advantage over the rat in generation of new transgenic models. Despite these limitations, transgenic rats have greatly expanded the range of potential experimental approaches. The large size of rats permits intrathecal administration of drugs, stem cell transplantation, serial sampling of the cerebrospinal fluid, microsurgical techniques, in vivo nerve recordings, and neuroimaging procedures. Moreover, the rat is routinely employed to demonstrate therapeutic efficacy and to assess toxicity of novel therapeutic compounds in drug development. Here we suggest that the rat constitutes a slightly underestimated but perspective animal model well-suited for understanding the mechanisms and pathways underlying the human neurodegenerative disorders.

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A transgenic rat expressing human APP with the Swedish Alzheimer’s disease mutation

Cited by 36 publications

References 21 publications

Modeling human neurodegenerative diseases in transgenic systems

Modeling human neurodegenerative diseases in transgenic systems

Coexisting Cholinergic and Parahippocampal Degeneration: A Key to Memory Loss in Dementia and a Challenge for Transgenic Models?

Beyond the Rat Models of Human Neurodegenerative Disorders

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