MODELING THE FERTILIZATION CALCIUM WAVE IN MOUSE EGGS

模拟小鼠卵中的受精钙波

• 批准号: 6657247
• 负责人: JOHN M WAGNER
• 金额: $ 4.62万
• 依托单位: UNIVERSITY OF CONNECTICUT SCH OF MED/DNT
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-11-01 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/6657247
• 关键词: bioengineering /biomedical engineering; calcium flux; egg /ovum; endoplasmic reticulum; fertilization; inositol phosphates; laboratory mouse; mathematical model; model design /development

The overall goal of this proposal is to develop a realistic spatial model of the mouse oocyte and egg, that will allow me to examine the mechanisms underlying maturation and fertilization. I will then use this model to answer a very simple question: what happens to the immature oocyte during maturation that makes it fertilizable, and once it is fertilized, how are these maturation-induced changes important for the ensuing calcium signal? It has been known for some time that during maturation, the oocyte increases its capability to release calcium, and a number of potential mechanisms have been proposed: l) an increase in the ER's calcium-sequestering capability; 2) an increase in the ER's ability to release calcium via an increase in the number and/or density of Ip3 receptors; 3) an increase in the ER's ability to sequester and/or release calcium differentially in specific spatial regions as a result of structural rearrangement of the ER; 4) an increase in total intracellular calcium due to influx; and 5) a change in the IP3 receptor sensitivity. By dint of the model's incorporation of both maturation and fertilization mechanisms, I will test these hypotheses by examining the effects of such changes on both the pre-fertilization and post-fertilization egg, and comparing them to experiment. Additionally, I will use the model to investigate the mechanisms underlying the initiation and propagation of the fertilization wave, in a manner similar to my previous work with Xenopus. Finally, I will perform limited laboratory experiments, when reasonable, to collect data for both model calibration and, possibly, comparison of simulation results, when such data are not available in the literature. The modeling and simulation will be performed in collaboration with Dr. Les Loew and others in CBIT, and the experimental work will be greatly aided by collaboration with members of Dr. Laurinda Jaffe's lab.

该提案的总体目标是开发小鼠卵母细胞和卵子的真实空间模型，这将使​​我能够检查成熟和受精的机制。然后，我将使用这个模型来回答一个非常简单的问题：未成熟的卵母细胞在成熟过程中发生了什么，使其能够受精，一旦受精，这些成熟引起的变化对于随后的钙信号有何重要意义？一段时间以来，人们已经知道，在成熟过程中，卵母细胞释放钙的能力会增强，并且已经提出了许多潜在的机制：l) ER 的钙隔离能力增强； 2) 通过增加 Ip3 受体的数量和/或密度来增加 ER 释放钙的能力； 3) 由于内质网结构重排，内质网在特定空间区域差异性地螯合和/或释放钙的能力增加； 4）由于内流导致细胞内总钙增加； 5) IP3受体敏感性的变化。通过该模型结合了成熟和受精机制，我将通过检查这些变化对受精前和受精后卵子的影响并将其与实验进行比较来检验这些假设。此外，我将使用该模型来研究受精波启动和传播的机制，类似于我之前对非洲爪蟾的研究。最后，在合理的情况下，我将进行有限的实验室实验，以收集模型校准数据，并可能在文献中没有此类数据时，收集模拟结果的比较数据。建模和仿真将与 CBIT 的 Les Loew 博士和其他人合作进行，与 Laurinda Jaffe 博士实验室成员的合作将极大地帮助实验工作。