A knock-in mouse model for male fertility: basis for the mammal-specific protein phosphatase isoform PP1y2 in sperm
雄性生育能力的敲入小鼠模型:精子中哺乳动物特异性蛋白磷酸酶亚型 PP1y2 的基础
基本信息
- 批准号:10675027
- 负责人:
- 金额:$ 7.6万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2022
- 资助国家:美国
- 起止时间:2022-08-01 至 2024-07-31
- 项目状态:已结题
- 来源:
- 关键词:AffectAlternative SplicingAmino Acid SequenceAnimalsBindingBiochemicalBrainCRISPR/Cas technologyCalcineurinCalciumCellsCharacteristicsClinicalComplexConsensusCouplesCyclic AMPCyclic AMP-Dependent Protein KinasesDevelopmentEnergy MetabolismEngineeringEnzymesEpididymisExonsFemaleFertilityGene ExpressionGenesGeneticGenomeGerm CellsGlycogen Synthase Kinase 3ImpairmentIn VitroInfertilityIntronsInvertebratesKnock-in MouseKnock-outKnockout MiceMale InfertilityMammalsMessenger RNAMetabolismMorphogenesisMusNucleotidesPenetrationPhenotypePhosphoproteinsPhysiological ProcessesProcessProtein IsoformsProtein phosphataseProteinsRNA SplicingRoleSecond Messenger SystemsSeminiferous tubule structureSignal TransductionSignaling ProteinSiteSomatic CellSperm MotilitySpermatogenesisSpermatogenic CellTestisTissuesTranscriptVertebratesWild Type Mousecell motilityegggenetic manipulationinorganic phosphateinsightknockout genemalemale fertilitymanmouse modelparalogous geneplacental mammalpromoterreproductive tractsperm cellsperm functionsperm proteintransgene expressionzygote
项目摘要
Spermatogenesis and the development of fertility competent sperm involve complex
processes in the testis, epididymis and female reproductive tract. These physiological processes
of sperm formation and development are difficult if not impossible to be recapitulated and studied
in vitro. Mouse models amenable to genetic manipulation are essential for understanding the basis
for male gamete function.
Considerable progress has been made in identifying signaling proteins essential for
sperm function which include components of cyclic AMP metabolism, proteins controlling sperm
intracellular pH and calcium levels of sperm in the epididymis and in the female reproductive tract.
Numerous gene knock out approaches targeting the signaling proteins involved in metabolism and
in the action of second messengers result in male infertility. Yet the mechanistic basis for normal
and disrupted sperm function remains largely unknown.
We discovered that a protein phosphatase PP12, which is one of two paralogs from
one gene Ppp1cc, is highly expressed in testis and present in sperm. The other paralog, PP11, is
expressed in brain and several somatic cells and tissues and cells. Two other genes encode the
PP1 and PP1 isoforms. These four PP1 isoforms are highly conserved between themselves and
across species. The isoform PP12 is present only in placental mammals suggesting an essential
role for it in the unique features of mammalian sperm function. It is notable that sperm from other
species contain one of the protein phosphate isoforms PP11, PP1 or PP1. The targeted knock
out of Ppp1cc results in male infertility. Transgenic expression of PP12, but not PP11, driven by
a testis specific promoter restores fertility in the Ppp1cc null mice, highlighting the essential
requirement for PP12. In this proposal we will examine a mouse line we have generated where
the Ppp1cc gene is edited by Crispr/Cas9 to express PP11 alone in testis. Determination of the
impaired functions in PP11 bearing mice and sperm should lead to the identification of key proteins
essential for normal sperm function.
Male infertility is responsible for about 10% of infertile couples. Identification of the
causes and treatments for male infertility are limited. A number of factors can affect male infertility:
major factors are likely environmental or genetic. This mouse model bearing the non-mammalian
PP1 isoform in sperm should also be valuable in not only understanding the significance of the
presence of PP12 in all mammals but also in understanding the biochemical basis for fertility and
infertility in man.
精子发生和生育能力精子的发育涉及复杂的过程
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
数据更新时间:{{ journalArticles.updateTime }}
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
数据更新时间:{{ journalArticles.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ monograph.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ sciAawards.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ conferencePapers.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ patent.updateTime }}
SRINIVASAN VIJAYARAGHAVAN其他文献
SRINIVASAN VIJAYARAGHAVAN的其他文献
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
{{ truncateString('SRINIVASAN VIJAYARAGHAVAN', 18)}}的其他基金
A knock-in mouse model for male fertility: basis for the mammal-specific protein phosphatase isoform PP1y2 in sperm
雄性生育能力的敲入小鼠模型:精子中哺乳动物特异性蛋白磷酸酶亚型 PP1y2 的基础
- 批准号:
10527437 - 财政年份:2022
- 资助金额:
$ 7.6万 - 项目类别:
Identification of Phospho-proteins Regulating Sperm Function
调节精子功能的磷酸蛋白的鉴定
- 批准号:
9333123 - 财政年份:2016
- 资助金额:
$ 7.6万 - 项目类别:
Protein Phosphatase Action in Mammalian Spermatogenesis and Sperm Function
蛋白磷酸酶在哺乳动物精子发生和精子功能中的作用
- 批准号:
8289861 - 财政年份:2012
- 资助金额:
$ 7.6万 - 项目类别:
Regulation of Sperm Function by Protein Phosphorylation
蛋白质磷酸化调节精子功能
- 批准号:
8051037 - 财政年份:2010
- 资助金额:
$ 7.6万 - 项目类别:
Regulation of Sperm Function by Protein Phosphorylation
蛋白质磷酸化调节精子功能
- 批准号:
7846469 - 财政年份:2009
- 资助金额:
$ 7.6万 - 项目类别:
The Role of 14-3-3 Proteins in Oogenesis and Early Development
14-3-3 蛋白在卵子发生和早期发育中的作用
- 批准号:
9170889 - 财政年份:2009
- 资助金额:
$ 7.6万 - 项目类别:
REGULATION OF SPERM FUNCTION BY PROTEIN PHOSPHORYLATION
蛋白质磷酸化对精子功能的调节
- 批准号:
6637061 - 财政年份:2001
- 资助金额:
$ 7.6万 - 项目类别:
REGULATION OF SPERM FUNCTION BY PROTEIN PHOSPHORYLATION
蛋白质磷酸化对精子功能的调节
- 批准号:
6521294 - 财政年份:2001
- 资助金额:
$ 7.6万 - 项目类别:
Regulation of Sperm Function by Protein Phosphorylation
蛋白质磷酸化调节精子功能
- 批准号:
7534804 - 财政年份:2001
- 资助金额:
$ 7.6万 - 项目类别:
Regulation of Sperm Function by Protein Phosphorylation
蛋白质磷酸化调节精子功能
- 批准号:
7659309 - 财政年份:2001
- 资助金额:
$ 7.6万 - 项目类别:
相似海外基金
Alternative splicing of Grin1 controls NMDA receptor function in physiological and disease processes
Grin1 的选择性剪接控制生理和疾病过程中的 NMDA 受体功能
- 批准号:
488788 - 财政年份:2023
- 资助金额:
$ 7.6万 - 项目类别:
Operating Grants
RBFOX2 deregulation promotes pancreatic cancer progression through alternative splicing
RBFOX2 失调通过选择性剪接促进胰腺癌进展
- 批准号:
10638347 - 财政年份:2023
- 资助金额:
$ 7.6万 - 项目类别:
Long Noncoding RNA H19 Mediating Alternative Splicing in ALD Pathogenesis
长非编码 RNA H19 介导 ALD 发病机制中的选择性剪接
- 批准号:
10717440 - 财政年份:2023
- 资助金额:
$ 7.6万 - 项目类别:
Using proteogenomics to assess the functional impact of alternative splicing events in glioblastoma
使用蛋白质基因组学评估选择性剪接事件对胶质母细胞瘤的功能影响
- 批准号:
10577186 - 财政年份:2023
- 资助金额:
$ 7.6万 - 项目类别:
Alternative splicing regulation of CLTC in the heart
心脏中 CLTC 的选择性剪接调节
- 批准号:
10749474 - 财政年份:2023
- 资助金额:
$ 7.6万 - 项目类别:
Nitric oxide as a novel regulator of alternative splicing
一氧化氮作为选择性剪接的新型调节剂
- 批准号:
10673458 - 财政年份:2023
- 资助金额:
$ 7.6万 - 项目类别:
Alternative splicing as an evolutionary driver of phenotypic plasticity
选择性剪接作为表型可塑性的进化驱动力
- 批准号:
2884151 - 财政年份:2023
- 资助金额:
$ 7.6万 - 项目类别:
Studentship
Rescuing SYNGAP1 haploinsufficiency by redirecting alternative splicing
通过重定向选择性剪接挽救 SYNGAP1 单倍体不足
- 批准号:
10660668 - 财政年份:2023
- 资助金额:
$ 7.6万 - 项目类别:
CAREER: Mechanotransduction, transcription, and alternative splicing in cell biology
职业:细胞生物学中的机械转导、转录和选择性剪接
- 批准号:
2239056 - 财政年份:2023
- 资助金额:
$ 7.6万 - 项目类别:
Continuing Grant
Investigating the role of alternative splicing in the islets of Langerhans in developing diabetes.
研究朗格汉斯岛中选择性剪接在糖尿病发生中的作用。
- 批准号:
468851650 - 财政年份:2022
- 资助金额:
$ 7.6万 - 项目类别:
Research Grants














{{item.name}}会员




