Role of DAX1 in Testis Determination and Function
Role of DAX1 in Testis Determination and Function
批准号:
7285191
负责人:
James Larry JAMESON
金额:
$30.0万
依托单位国家:
美国
项目类别:
财政年份:
2003
资助国家:
美国
项目状态:
已结题
起止时间:
2003-09-11 至 2008-06-30
关键词:
AdultAnimal ModelBackcrossingsBindingBinding SitesBiological AssayCandidate Disease GeneComplexDNADevelopmentDoctor of PhilosophyEmbryoExhibitsFemaleGene DosageGene DuplicationGene ExpressionGene TargetingGenesGeneticGenetic TranscriptionGoalsGonadal structureGrantHistologicImmunoprecipitationKnock-outLibrariesLinkMale InfertilityMammalsMediatingModelingMolecularMusMutagenesisMutationNuclear Orphan ReceptorOther GeneticsOvarianPathway interactionsPatientsPhenotypePlayProteinsRegulationRepressionRoleSF1StructureStudy modelsTestisTranscription Repressor/CorepressorTwo-Hybrid System TechniquesYeastsbasecell typechromatin immunoprecipitationdesigngene repressionin vivoinsightmalemouse modelnovelpromoterprotein protein interactionsexsex determinationsuccesstranscription factoryeast two hybrid system
中文摘要
在过去的8年里,我们发现并鉴定了患有自然突变的患者
英文摘要
Over the last 8 years, we identified and characterized patients with naturally occurring mutations in
the orphan nuclear receptors, DAXl and SF1, and demonstrated that DAXl acts in part by inhibiting SF1-
mediated transcription. Using targeted mutagenesis, we developed a murine Daxl knockout (KO) model and
identified roles for Daxl in gonadal determination, testis development, and adult testis function. In this grant,
we propose to extend these studies, which have provided unexpected insight into mechanisms of gonadal
development. We propose 3 inter-related aims that focus on Daxl structure and function as a transcriptional
represser, identify genetic pathways regulated by Daxl, and develop animal models to unravel the interplay
of Daxl with other genes involved in testis development and function. Specifically, in Aim 1 we will identify
molecular partners that mediate DAXl transcriptional repression. Naturally occurring DAX1 mutations
will be identified and characterized to elucidate key structural domains required for DAX1 function in vivo.
Candidate proteins identified in a yeast two-hybrid screen of an embryonic gonadal library will be further
characterized. The goal of Aim 2 is to identify the genetic pathways regulated by Daxl using microarray
analyses of genes expressed in wild type versus Daxl-deficient embryonic gonads at 12 dpc, a timepoint
when Daxl expression diverges in males and females. Aim 3 is designed to explore the interaction of
Daxl with other genetic pathways in vivo. Using mice that lack Daxl, we will explore the gonadal
phenotypes of mice with selective rescue of Daxl in various cell types. In addition, Daxl-deficient mice will
be crossed to other strains with alterations in genetic pathways proposed to intersect with Daxl (e.g., Sfl,
Sry, Ptc). Success in these aims should provide a critical link between DAX1 and transcriptional repression
pathways that link a variety of other transcription factors involved in gonadal development.
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DOI:
10.1016/j.mce.2011.04.017
发表时间:
2011-10-22
期刊:
MOLECULAR AND CELLULAR ENDOCRINOLOGY
影响因子:
4.1
作者:
[Jadhav, Unmesh, Harris, Rebecca M., Jameson, J. Larry]
通讯作者:
Jameson, J. Larry
X-linked sex-determining region Y box 3 (SOX3) gene mutations are uncommon in men with idiopathic oligoazoospermic infertility.
X 连锁性别决定区 Y 框 3 (SOX3) 基因突变在特发性少精症不育症男性中并不常见。
DOI:
10.1210/jc.2004-0191
发表时间:
2004
期刊:
The Journal of clinical endocrinology and metabolism.
影响因子:
--
作者:
[Raverot,Gerald, Lejeune,Herve, Kotlar,Tom, Pugeat,Michel, Jameson,JLarry]
通讯作者:
Jameson,JLarry
DOI:
10.1210/jc.2006-0603
发表时间:
2006-08
期刊:
The Journal of clinical endocrinology and metabolism
影响因子:
--
作者:
[Lin L, Gu WX, Ozisik G, To WS, Owen CJ, Jameson JL, Achermann JC]
通讯作者:
Achermann JC
Heterozygous missense mutations in steroidogenic factor 1 (SF1/Ad4BP, NR5A1) are associated with 46,XY disorders of sex development with normal adrenal function.
类固醇生成因子1(SF1/AD4BP,NR5A1)中的杂合错义突变与46个,性别发展的XY疾病具有正常的肾上腺功能。
DOI:
10.1210/jc.2006-1672
发表时间:
2007-03
期刊:
The Journal of clinical endocrinology and metabolism
影响因子:
--
作者:
[Lin L, Philibert P, Ferraz-de-Souza B, Kelberman D, Homfray T, Albanese A, Molini V, Sebire NJ, Einaudi S, Conway GS, Hughes IA, Jameson JL, Sultan C, Dattani MT, Achermann JC]
通讯作者:
Achermann JC
Career Development in Women's Health (CDWH)
-
批准号:7288480
-
项目类别:
-
资助金额:$50.0万
-
财政年份:2007
-
负责人:James Larry JAMESON
-
依托单位:
Role of DAX1 in Testis Determination and Function
-
批准号:6800745
-
项目类别:
-
资助金额:$31.27万
-
财政年份:2003
-
负责人:James Larry JAMESON
-
依托单位:
NONCLASSICAL ESTROGEN RECEPTOR ALPHA ACTION IN THE OVARY
-
批准号:6849152
-
项目类别:
-
资助金额:$25.0万
-
财政年份:2003
-
负责人:James Larry JAMESON
-
依托单位:
DAX1 in Testis Determination and Function
-
批准号:6675743
-
项目类别:
-
资助金额:$31.36万
-
财政年份:2003
-
负责人:James Larry JAMESON
-
依托单位:
Role of DAX1 in Testis Determination and Function
-
批准号:7069596
-
项目类别:
-
资助金额:$30.73万
-
财政年份:2003
-
负责人:James Larry JAMESON
-
依托单位:
Role of DAX1 in Testis Determination and Function
-
批准号:6914899
-
项目类别:
-
资助金额:$31.27万
-
财政年份:2003
-
负责人:James Larry JAMESON
-
依托单位:
Identify Sex Determination Genes By ENU Mutagenesis
-
批准号:6575039
-
项目类别:
-
资助金额:$50.87万
-
财政年份:2002
-
负责人:James Larry JAMESON
-
依托单位:
Identify Sex Determination Genes By ENU Mutagenesis
-
批准号:6797305
-
项目类别:
-
资助金额:$48.89万
-
财政年份:2002
-
负责人:James Larry JAMESON
-
依托单位:
Identify Sex Determination Genes By ENU Mutagenesis
-
批准号:6668469
-
项目类别:
-
资助金额:$47.31万
-
财政年份:2002
-
负责人:James Larry JAMESON
-
依托单位:
Identify Sex Determination Genes By ENU Mutagenesis
-
批准号:6946366
-
项目类别:
-
资助金额:$50.24万
-
财政年份:2002
-
负责人:James Larry JAMESON
-
依托单位:
MOLECULAR BASIS OF DEFECTS IN GONADOTROPIN BIOSYNTHESIS
-
批准号:6583743
-
项目类别:
-
资助金额:$23.61万
-
财政年份:2002
-
负责人:James Larry JAMESON
-
依托单位:
Identify Sex Determination Genes By ENU Mutagenesis
-
批准号:7070557
-
项目类别:
-
资助金额:$50.43万
-
财政年份:2002
-
负责人:James Larry JAMESON
-
依托单位:
MOLECULAR BASIS OF DEFECTS IN GONADOTROPIN BIOSYNTHESIS
-
批准号:6564721
-
项目类别:
-
资助金额:$23.61万
-
财政年份:2001
-
负责人:James Larry JAMESON
-
依托单位:
MOLECULAR BASIS OF DEFECTS IN GONADOTROPIN BIOSYNTHESIS
-
批准号:6429998
-
项目类别:
-
资助金额:$23.61万
-
财政年份:2000
-
负责人:James Larry JAMESON
-
依托单位:
MOLECULAR BASIS OF DEFECTS IN GONADOTROPIN BIOSYNTHESIS
-
批准号:6424539
-
项目类别:
-
资助金额:$23.06万
-
财政年份:2000
-
负责人:James Larry JAMESON
-
依托单位:
ROLE OF SF1 AND DAX1 IN OVARIAN FUNCTION
-
批准号:6410468
-
项目类别:
-
资助金额:$17.7万
-
财政年份:2000
-
负责人:James Larry JAMESON
-
依托单位:
ROLE OF SF1 AND DAX1 IN OVARIAN FUNCTION
-
批准号:6301923
-
项目类别:
-
资助金额:$13.55万
-
财政年份:1999
-
负责人:James Larry JAMESON
-
依托单位:
MOLECULAR BASIS OF DEFECTS IN GONADOTROPIN BIOSYNTHESIS
-
批准号:6395942
-
项目类别:
-
资助金额:$28.05万
-
财政年份:1999
-
负责人:James Larry JAMESON
-
依托单位:
ROLE FOR FKBP12 IN GNRH SIGNALING
-
批准号:2889497
-
项目类别:
-
资助金额:$7.4万
-
财政年份:1998
-
负责人:James Larry JAMESON
-
依托单位:
ROLE OF SF1 AND DAX1 IN OVARIAN FUNCTION
-
批准号:6108458
-
项目类别:
-
资助金额:$13.55万
-
财政年份:1998
-
负责人:James Larry JAMESON
-
依托单位:
海外基金