Forkhead Factor, FOXL2, in Pituitary Development

叉头因子 FOXL2 在垂体发育中的作用

基本信息

批准号：
6856547
负责人：
Buffy Sue Ellsworth
金额：
$ 4.83万
依托单位：
UNIVERSITY OF MICHIGAN AT ANN ARBOR
依托单位国家：
美国
项目类别：
财政年份：
2004
资助国家：
美国
起止时间：
2004-04-30 至 2006-04-29
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/6856547
关键词：
enzyme mechanism gel mobility shift assay gene expression gene mutation gene targeting genetic regulatory element genetically modified animals histogenesis in situ hybridization laboratory mouse pituitary gland postdoctoral investigator tissue /cell culture transcription factor transfection /expression vector

项目摘要

DESCRIPTION (provided by applicant): Foxl-2 is expressed in the developing eye and in the adult ovary and is required for normal development and function of these organs in humans. Recently, expression of FoxL2 has been detected in the developing mouse pituitary from e10.5 to el 5. To examine the role of FOXL2 in pituitary development, the following studies will be performed: characterize the developmental expression of Foxl2 and place it in the genetic hierarchy of pituitary developmental control, define important regulatory sequences for Foxl2 expression in cell culture and transgenic mice, and examine the role of FOXL2 in the developing anterior pituitary by generation of gain and loss of function alleles. In situ hybridization of pituitaries from normal mice will be used to characterize Foxl2 expression. Normal expression patterns for Foxl2 will be compared to those in mice with mutations in critical pituitary transcription factors. This information will place FOXL2 in the genetic hierarchy. Transient transfections of mammalian cells and electrophoretic mobility shift assays will be used to define the minimal essential sequence for Foxl2 expression and to test for direct regulation by factors that are upstream of Foxl2 in the genetic hierarchy. These findings will be confirmed in transgenic animals. To delineate the role of FOXL2 in pituitary development, FoxL2 will be over-expressed and will be disrupted specifically in the pituitaries of mice, allowing us to separate the role of FOXI.2 in the pituitary from its role in other organs.

描述（由申请人提供）：FOXL-2在发育中的眼睛和成年卵巢中表达，是这些器官在人类中的正常发育和功能所必需的。 Recently, expression of FoxL2 has been detected in the developing mouse pituitary from e10.5 to el 5. To examine the role of FOXL2 in pituitary development, the following studies will be performed: characterize the developmental expression of Foxl2 and place it in the genetic hierarchy of pituitary developmental control, define important regulatory sequences for Foxl2 expression in cell culture and transgenic mice, and examine the role of FOXL2 in the developing anterior pituitary通过产生增益和功能等位基因的损失。正常小鼠的垂体的原位杂交将用于表征FOXL2表达。 FOXL2的正常表达模式将与关键垂体转录因子中突变的小鼠中的正常表达模式进行比较。此信息将使FOXL2置于遗传层次结构中。哺乳动物细胞和电泳迁移率转移测定法的瞬时转染将用于定义FOXL2表达的最小基本序列，并通过遗传层次结构中FOXL2上游的因素来测试直接调控。这些发现将在转基因动物中得到证实。为了描述FOXL2在垂体发展中的作用，FOXL2将被过表达，并将在小鼠的垂体中特别受到破坏，从而使我们能够将foxi.2在垂体中的作用与其他器官的作用分开。