Human apoB overexpression and a high-cholesterol diet differently modify the brain APP metabolism in the transgenic mouse model of atherosclerosis

Bjelik, Annamária; Bereczki, Erika; Gonda, Szilvia; Juhász, Anna; Rimanóczy, Ágnes; Zana, Marianna; Csont, Tamás; Pákáski, Magdolna; Boda, Krisztina; Ferdinándy, Péter; Puskás, László G.; Janka, Zoltán; Sántha, Miklós; Kálmán, János

doi:10.1016/j.neuint.2006.01.026

Cited by 36 publications

(34 citation statements)

References 36 publications

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“…Insertion of the apoB-100 gene into mice creates a sharp increase in plasma LDL after a high-fat diet, a lipid profile similar to what has been seen in humans (Bjelik et al, 2006; Purcell-Huynh et al, 1995). The apoB100 transgenic mice have higher serum total and LDL cholesterol and a statistically significant cholesterol-dependent increase in Bruch’s membrane thickness (Sallo et al, 2009).…”

Section: Murine Models Of Dry Amdmentioning

confidence: 56%

Retinal ultrastructure of murine models of dry age-related macular degeneration (AMD)

Ramkumar

Zhang

Chan

2010

Progress in Retinal and Eye Research

134

123

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Age-related macular degeneration (AMD) is the most prevalent form of irreversible blindness worldwide in the elderly population. The pathology of dry AMD consists of degeneration of photoreceptors and the RPE, lipofuscin (A2E) accumulation, and drusen formation. Mice have been widely used for generating models that simulate human AMD features for investigating the pathogenesis, treatment and prevention of the disease. Although the mouse has no macula, focal atrophy of photorecptors and RPE, lipofuscin accumulation, and increased A2E can develop in aged mouse eyes. However, drusen are rarely seen in mice because of their simpler Bruch's membrane and different process of lipofuscin extrusion compared with humans. Thus, analyzing basal deposits at the ultrastructural level and understanding the ultrastructural pathologic differences between various mouse AMD models are critical to comprehending the significance of research findings and response to possible therapeutic options for dry AMD.Based on the multifactorial pathogenesis of AMD, murine dry AMD models can be classified into three groups. First, genetically engineered mice that target genes related to juvenile macular dystrophies are the most common models, and they include abcr −/− (Stargardt disease), transgenic ELOVL4 (Stargardt-3 dominant inheritary disease), Efemp1 R345W/R345W (Doyne honeycomb retinal dystrophy), and Timp3 S156C/S156C (Sorsby fundus dystrophy) mice. Other murine models target genes relevant to AMD, including inflammatory genes such as Cfh −/− , Ccl2 −/− , Ccr2 −/− , Cx3cr1 −/− , and Ccl2 −/− /cx3cr1 −/− , oxidative stress associated genes such as Sod1 −/− and Sod2 knockdown, metabolic pathway genes such as neprilysin −/− (amyloid β), transgenic mcd/mcd (cathepsin D), Cp −/− /Heph −/Y (ferroxidase ceruloplasmin/hepaestin, iron metabolism), and transgenic ApoE4 on high fat and high cholesterol diet (lipid metabolism). Second, mice have also been immunologically manipulated by immunization with carboxyethylpyrrole (CEP), an oxidative fragment of DHA found in drusen, and found to present with dry AMD features. Third, natural mouse strains such as arrd2/arrd2 (Mdm gene mutation) and the senescence accelerated mice (SAM) spontaneously develop features of dry AMD like photoreceptor atrophy and thickening of Bruch's membrane.Corresponding author: Chi-Chao Chan, MD, 10 Center Drive, 10/10N103, NIH/NEI, Bethesda, MD 20892-1857. Tel: (301), 496-0417, Fax: (301) 402-8664, chanc@nei.nih.gov. Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. NIH Public AccessAuthor Manuscript Prog Retin Eye Res. Author ma...

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Section: Murine Models Of Dry Amdmentioning

confidence: 56%

Retinal ultrastructure of murine models of dry age-related macular degeneration (AMD)

Ramkumar

Zhang

Chan

2010

Progress in Retinal and Eye Research

134

123

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“…Transgenic mice overexpressing human apoB-100 protein were generated as described earlier [22]. Briefly, fertilized oocytes of C57/B6 × CBA F1 females were collected and injected with the purified P1-phagemid DNA containing the entire 43 kb human apoB-100 gene, the 19 kb of the 5′ and the 14 kb of the 3′ flanking genomic sequences [20] in a concentration of 1 ng/ml, according to a standard technique [23].…”

Section: Animals Diets Experimental Groupsmentioning

confidence: 99%

“…Briefly, fertilized oocytes of C57/B6 × CBA F1 females were collected and injected with the purified P1-phagemid DNA containing the entire 43 kb human apoB-100 gene, the 19 kb of the 5′ and the 14 kb of the 3′ flanking genomic sequences [20] in a concentration of 1 ng/ml, according to a standard technique [23]. Tail DNA of 10-day-old pups was purified [22], and integrated transgenes were detected by PCR, using primers from the 5′ promoter region of human apoB gene [20]. The expression of human apoB-100 transgene was detected by using real-time RT-PCR and Western blot analysis.…”

Section: Animals Diets Experimental Groupsmentioning

confidence: 99%

Hypercholesterolemia increases myocardial oxidative and nitrosative stress thereby leading to cardiac dysfunction in apoB-100 transgenic mice

Csont

Bereczki

Bencsik

et al. 2007

Cardiovascular Research

101

113

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“…Previously, we generated a transgenic mouse strain overexpressing the human ApoB-100 protein [16]. On a standard diet, elevated serum triglyceride level, on cholesterol high diet an increased serum total cholesterol level and coronary atherosclerosis were observed [17].…”

Section: Introductionmentioning

confidence: 99%

Increased Tau Phosphorylation and Impaired Presynaptic Function in Hypertriglyceridemic ApoB-100 Transgenic Mice

et al. 2012

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AimsApoB-100 is the major protein component of cholesterol- and triglyceride-rich LDL and VLDL lipoproteins in the serum. Previously, we generated and partially described transgenic mice overexpressing the human ApoB-100 protein. Here, we further characterize this transgenic strain in order to reveal a possible link between hypeprlipidemia and neurodegeneration.Methods and ResultsWe analyzed the serum and cerebral lipid profiles, tau phosphorylation patterns, amyloid plaque-formation, neuronal apoptosis and synaptic plasticity of young (3 month old), adult (6 month old) and aging (10–11 month old) transgenic mice. We show that ApoB-100 transgenic animals present i) elevated serum and cerebral levels of triglycerides and ApoB-100, ii) increased cerebral tau phosphorylation at phosphosites Ser199, Ser199/202, Ser396 and Ser404. Furthermore, we demonstrate, that tau hyperphosphorylation is accompanied by impaired presynaptic function, long-term potentiation and widespread hippocampal neuronal apoptosis.ConclusionsThe results presented here indicate that elevated ApoB-100 level and the consequent chronic hypertriglyceridemia may lead to impaired neuronal function and neurodegeneration, possibly via hyperphosphorylation of tau protein. On account of their specific phenotype, ApoB-100 transgenic mice may be considered a versatile model of hyperlipidemia-induced age-related neurodegeneration.

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Human apoB overexpression and a high-cholesterol diet differently modify the brain APP metabolism in the transgenic mouse model of atherosclerosis

Cited by 36 publications

References 36 publications

Retinal ultrastructure of murine models of dry age-related macular degeneration (AMD)

Retinal ultrastructure of murine models of dry age-related macular degeneration (AMD)

Hypercholesterolemia increases myocardial oxidative and nitrosative stress thereby leading to cardiac dysfunction in apoB-100 transgenic mice

Increased Tau Phosphorylation and Impaired Presynaptic Function in Hypertriglyceridemic ApoB-100 Transgenic Mice

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