Hyperlipidemia induces typical atherosclerosis development in Ldlr and Apoe deficient rats

Zhao, Yongliang; Yang, Yi‐Qing; Xing, Roumei; Cui, Xueqin; Xiao, Yufang; Xie, Ling; You, Panpan; Wang, Tongtong; Zeng, Li; Peng, Wenhui; Li, Dali; Chen, Huaqing; Liu, Mingyao

doi:10.1016/j.atherosclerosis.2018.02.015

Cited by 82 publications

(75 citation statements)

References 36 publications

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“…This study shows that targeting APOE in various CNS cell types can lead to beneficial functional alterations in patient-derived in vitro systems. In animal models, CRISPR/Cas9 is relatively safe and has been successfully used to generate APOE KO in pigs and rats with little to no off-target incidents or mosaicism [159][160][161]. However, there is always the possibility of unexpected edits in the targeted and non-targeted portions of the genome leading to unanticipated side effects as well as triggering cancer risk [162,163].…”

Section: Crispr/cas9 Mediated Gene Editingmentioning

confidence: 99%

Therapeutic approaches targeting Apolipoprotein E function in Alzheimer’s disease

Williams

Borchelt

Chakrabarty

2020

Mol Neurodegeneration

111

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One of the primary genetic risk factors for Alzheimer's disease (AD) is the presence of the Ɛ4 allele of apolipoprotein E (APOE). APOE is a polymorphic lipoprotein that is a major cholesterol carrier in the brain. It is also involved in various cellular functions such as neuronal signaling, neuroinflammation and glucose metabolism. Humans predominantly possess three different allelic variants of APOE, termed E2, E3, and E4, with the E3 allele being the most common. The presence of the E4 allele is associated with increased risk of AD whereas E2 reduces the risk. To understand the molecular mechanisms that underlie APOE-related genetic risk, considerable effort has been devoted towards developing cellular and animal models. Data from these models indicate that APOE4 exacerbates amyloid β plaque burden in a dose-dependent manner. and may also enhance tau pathogenesis in an isoform-dependent manner. Other studies have suggested APOE4 increases the risk of AD by mechanisms that are distinct from modulation of Aβ or tau pathology. Further, whether plasma APOE, by influencing systemic metabolic pathways, can also possibly alter CNS function indirectly is not complete;y understood. Collectively, the available studies suggest that APOE may impact multiple signaling pathways and thus investigators have sought therapeutics that would disrupt pathological functions of APOE while preserving or enhancing beneficial functions. This review will highlight some of the therapeutic strategies that are currently being pursued to target APOE4 towards preventing or treating AD and we will discuss additional strategies that holds promise for the future.

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Section: Crispr/cas9 Mediated Gene Editingmentioning

confidence: 99%

Therapeutic approaches targeting Apolipoprotein E function in Alzheimer’s disease

Williams

Borchelt

Chakrabarty

2020

Mol Neurodegeneration

111

View full text Add to dashboard Cite

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“…Fatty liver phenotypes similar to those observed in Ldlr-edited mice were also found in rats upon CRISPR/Cas9-mediated deletion of apolipoprotein E (Apoe). 73 ApoE is a component of lipoprotein remnants; its deficiency in humans leads to decreased clearance of remnants and an increased risk of atherosclerosis, a condition known as familial dysbetalipoproteinemia. 74 CRISPR/Cas9mediated deletion of Ldlr and Apoe (either individually or in combination) was achieved by zygote microinjection of sgRNA and Cas9 mRNA, generating adult rats that exhibit hypercholesterolemia, hepatic steatosis, and atherosclerosis.…”

Section: Familial Hypercholesterolemiamentioning

confidence: 99%

“…74 CRISPR/Cas9mediated deletion of Ldlr and Apoe (either individually or in combination) was achieved by zygote microinjection of sgRNA and Cas9 mRNA, generating adult rats that exhibit hypercholesterolemia, hepatic steatosis, and atherosclerosis. 73 Primary hyperoxaluria type I disease Recently, Zheng et al generated a rat model of primary hyperoxaluria type I disease. 75 The authors deleted alanine-glyoxylate aminotransferase in rat zygotes, resulting in severe nephrocalcinosis due to the formation of oxalate crystals, as seen in humans.…”

Section: Familial Hypercholesterolemiamentioning

confidence: 99%

Using CRISPR/Cas9 to model human liver disease

et al. 2019

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CRISPR/Cas9 gene editing has revolutionised biomedical research. The ease of design has allowed many groups to apply this technology for disease modelling in animals. While the mouse remains the most commonly used organism for embryonic editing, CRISPR is now increasingly performed with high efficiency in other species. The liver is also amenable to somatic genome editing, and some delivery methods already allow for efficient editing in the whole liver. In this review, we describe CRISPR-edited animals developed for modelling a broad range of human liver disorders, such as acquired and inherited hepatic metabolic diseases and liver cancers. CRISPR has greatly expanded the repertoire of animal models available for the study of human liver disease, advancing our understanding of their pathophysiology and providing new opportunities to develop novel therapeutic approaches.

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“…For example, polymorphisms in the ARHGap42 gene, the PHACTR1 gene and the long‐noncoding RNA, termed Rffl‐lnc1 have been identified as potential therapeutic targets to alleviate hypertension. Knockout animals for genes such as Apolipoprotein E, the LDL receptor, leptin, and PCSK9 are currently being evaluated for their role in cardiovascular disease and diabetes.…”

Section: Genome Editingmentioning

confidence: 99%

Are We There Yet? How and When Specific Biotechnologies Will Improve Human Health

O’Day

Hosta‐Rigau

Oyarzún

et al. 2018

Biotechnology Journal

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Hyperlipidemia induces typical atherosclerosis development in Ldlr and Apoe deficient rats

Cited by 82 publications

References 36 publications

Therapeutic approaches targeting Apolipoprotein E function in Alzheimer’s disease

Therapeutic approaches targeting Apolipoprotein E function in Alzheimer’s disease

Using CRISPR/Cas9 to model human liver disease

Are We There Yet? How and When Specific Biotechnologies Will Improve Human Health

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