CORE--MOUSE GENETICS

描述（由申请人提供）： DRTC小鼠模型核心的主要目标是为 建立、维持和实验1型和2型糖尿病及相关疾病的小鼠模型，以协助DRTC研究人员实现其研究目标。核心的具体目标是：1.生产标准实验室品系的转基因小鼠;在NOD小鼠背景下生产转基因小鼠; 3.在标准和NOD背景下产生携带细菌人工染色体（BAC）的转基因小鼠; 4.提供标准化的ES细胞，协助生产基因靶向克隆; 5.建立基因靶向程序，用于靶向来自NOD x 129 F1小鼠的胚胎干（ES）干细胞系中的NOD染色体，促进基因敲除和敲入小鼠的产生，所述基因敲除和敲入小鼠可以在NOD中快速近交至纯合性; 6.通过标准和NOD ES细胞克隆的胚泡注射产生基因靶向小鼠;和7.与斯坦福大学的基因陷阱资源提供联系，促进DTRC成员筛选与I型和II型糖尿病相关的表型的小鼠插入突变。为了实现这些目标，核心将以类似于大多数机构转基因和靶向诱变核心的方式操作。这 然而，该基金将强调并具体支持与糖尿病有关的项目。例如，该核心将建立常规显微注射和基因靶向程序，使用来自NOD（和潜在的其他）小鼠品系的受精卵和胚胎干（ES）细胞系，这对糖尿病研究具有关键意义。该中心将进口和维持与糖尿病研究相关的小鼠品系和胚胎干细胞系，并将建立获得新的胚胎干细胞系的能力，以补充外部来源。此外，核心将订阅一个区域联盟，该联盟通过“基因陷阱”插入技术在小鼠中产生新的突变，以识别新的突变小鼠，这些小鼠表现出与UCSF DRTC在I型和II型糖尿病中的研究相关的发育或生理表型。核心的一个主要重点将是建立通过转基因和基因靶向实验遗传操纵非肥胖糖尿病（NOD）小鼠的能力。

DESCRIPTION (Provided by applicant): The primary objective of the DRTC Mouse Models Core is to create a shared resource for the establishment, maintenance and experimentation on mouse models of type 1 and type 2 diabetes and related disorders to assist DRTC investigators in meeting their research objectives. Specific aims of the core are: 1.Produce transgenic mice in standard laboratory strains; 2. Produce transgenic mice in the NOD mouse background; 3. Produce transgenic mice carrying bacterial artificial chromosomes (BACs), in standard and NOD backgrounds; 4. Provide standardized ES cells and assistance with producing gene targeted clones; 5. Establish gene-targeting procedures for targeting the NOD chromosomes in embryonic stem (ES) stern cell lines derived from NOD x 129 F1 mice, facilitating the generation of gene knockout and knock-in mice that can be rapidly inbred to homozygosity in NOD; 6. Produce gene targeted mice via blastocyst injection of standard and NOD ES cell clones; and 7. Provide liaison to the Stanford University Gene Trap Resource, facilitating the screening by DTRC members for mouse insertional mutations with phenotypes relevant to types I and II diabetes. To meet these aims, the core will operate in a fashion similar to most institutional transgenic and targeted mutagenesis cores. This facility will, however, emphasize and specifically support diabetes-related projects. For example, the core will establish routine microinjection and gene-targeting procedures using zygotes and embryonic stem (ES) cell lines from the NOD (and potentially other) mouse strains that are of key significance for diabetes research. The Core will import and maintain relevant mouse strains and ES cell lines relevant in diabetes research and it will establish the capability to derive new ES lines to complement external sources. In addition, the Core will subscribe to a regional consortium that is producing new mutations in the mouse through 'gene-trap' insertion technologies, so as to identify new mutant mice showing developmental or physiological phenotypes relevant to research of the UCSF DRTC in types I and II diabetes. A major focus of the core will be on establishing the capability to genetically manipulate the non-obese diabetic (NOD) mouse via transgenic and gene targeting experiments.