哈雷金老鼠突变降低了诱导亡的因子.
Jeffrey A Klein1, Chantal M Longo-Guess, Marlies P Rossmann
1The Jackson Laboratory, 600 Main Street, Bar Harbor, Maine 04609, USA.
Nature
|September 28, 2002
概括
哈勒金突变通过减少诱导亡因子 (AIF) 表达而导致神经退行,导致小鼠的氧化应激和细胞死亡. 恢复AIF水平保护神经元,突出其在预防神经退行性疾病中的作用.
科学领域:
- 神经科学是一个神经科学.
- 遗传学 是一个遗传学.
- 细胞生物学 细胞生物学
背景情况:
- 哈雷金 (Hq) 突变小鼠表现出小脑和视网膜神经元的渐进性退化.
- Hq突变与诱导亡因子 (AIF) 表达的显著减少有关.
研究的目的:
- 在Hq突变小鼠中确定神经退行的遗传原因.
- 研究诱导亡因子 (AIF) 在神经元生存和氧化应激中的作用.
主要方法:
- 基因分析以确定Hq突变.
- 在突变和野生类型小鼠中评估AIF表达水平.
- 在体外和体内实验来评估神经元对氧化应激的敏感性和AIF的影响.
- 对受损神经元中细胞循环重新进入的分析.
主要成果:
- Hq突变是Aif基因中的前病毒插入,将AIF表达率降低约80%.
- 突变的小脑颗粒细胞对过氧化物诱导的亡敏感,但可以通过AIF来拯救.
- 过度表达AIF减少野生类型细胞中过氧化物介导的细胞死亡,表明自由基清除功能.
- 在Hq小鼠中死亡的神经元显示氧化应激,并在细胞亡之前重新进入细胞循环.
结论:
- AIF在保护神经元免受氧化应激和预防细胞亡方面发挥着至关重要的作用.
- Hq小鼠作为氧化压力介导的神经退行症的遗传模型.
- 神经细胞循环的重新进入与衰老中枢神经系统中的氧化应激有关.
更多相关视频
相关概念视频
In-vitro Mutagenesis
14.8K
To learn more about the function of a gene, researchers can observe what happens when the gene is inactivated or “knocked out,” by creating genetically engineered knockout animals. Knockout mice have been particularly useful as models for human diseases such as cancer, Parkinson’s disease, and diabetes.
14.8K
Hedgehog Signaling Pathway
7.1K
The Hedgehog gene (Hh) was first discovered due to its control of the growth of disorganized, hair-like bristles phenotype in Drosophila, much like hedgehog spines. Hh plays a crucial role in the development of organs and the maintenance of homeostasis in both invertebrates and vertebrates. However, while Drosophila has only one Hh protein, mammals have multiple functional Hedgehog proteins - Sonic (Shh), Desert (Dhh), and Indian Hedgehog (Ihh). All of these homologous proteins have adapted to...
7.1K
Mouse Models of Cancer Study
4.7K
Mice have long served as models for studying human biology and pathology because of their phylogenetic and physiological similarity with humans. They are also easy to maintain and breed in the laboratory, and hence, many inbred strains are now available for research. Studies on mice have contributed immeasurably to our understanding of cancer biology.
The development of transgenic, knockout, and knock-in mice has led to an exponential increase in their use as model organisms in research,...
The development of transgenic, knockout, and knock-in mice has led to an exponential increase in their use as model organisms in research,...
4.7K
Caspases
8.7K
Caspase, a family of cysteine proteases, serve as effectors in apoptosis. The ced3 gene in C.elegans was first identified to be involved in apoptosis. This gene encodes the ced-3 caspase that is similar to the interleukin-1-beta converting enzyme or ICE in mammals. In addition to apoptosis, caspases also function in the inflammatory response. Inflammatory caspases are essential in activating pro-inflammatory cytokines that recruit immune cells and block the replication of pathogens inside...
8.7K
The Extrinsic Apoptotic Pathway
6.2K
The extrinsic apoptotic pathway is initiated when extracellular death-inducing signals, such as specific cytokines, activate the death receptors expressed on the cell surface. The immune cells involved in this pathway are natural killer cells (NK cells) and cytotoxic T-lymphocytes. NK cells are critical in innate immune response, while cytotoxic T-lymphocytes are associated with adaptive immune response. These cells recognize specific receptors expressed on the altered cells and activate...
6.2K
The Intrinsic Apoptotic Pathway
6.2K
Internal cellular stress, such as cellular injury or hypoxia, triggers intrinsic apoptosis. The B-cell lymphoma 2 (Bcl-2) family of proteins are the primary regulators of the intrinsic apoptotic pathway. For example, during DNA damage, checkpoint proteins, such as Ataxia Telangiectasia Mutated (ATM protein) and Checkpoints Factor-2 (Chk2) proteins, are activated. These proteins phosphorylate p53 which further activates pro-apoptotic proteins, such as Bax, Bak, PUMA, and Noxa, and inhibits...
6.2K


