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Dissect Assembly Rules of SPET12 Complex in the Mammalian Sperm

NCT04159402 · Status: COMPLETED · Type: OBSERVATIONAL · Enrollment: 183

Last updated 2022-10-04

No results posted yet for this study

Summary

The sperm of the KO mouse shothe investigatorsd severe defects of all found compartments: acrosome, nucleus, midpiece and tail. The investigators also found SEPT12 co-localizes and interact with SEPT1, 2, 4, 6, 7, 10, 11, and 14 in sperm. Interestingly, some of these septins form filaments with SEPT12 in cells. Based on these findings, it is hypothesized that (1) The core complex of SEPT12 filament consists of SEPT12-7-6-2-2-6-7-12; (2) Septin12 mutations, genetic variants, as the investigatorsll as haploinsufficiency disrupt SEPT12 filament and macro-complex; (3) Other SEPT's (e.g. SETP4, SEPT14) are also involved in the functionality of SEPT12; and (4) SEPT12 macro-complex is critical for compartment formation during terminal differentiation of male germ cells. The proposed study is designed to confirm the above hypotheses, to deconstruct mammalian SEPT12 complex, and to elucidate the functional significance of Septin12 mutations. In the proposed study, the investigators will use different methods, including proteomics, immunofluorescence assay, co- immunoprecipitation, pull-down assay, protein domain mapping, and protein complex fractionation to test the above hypothesis. The investigators have created a mouse carrying an important Septin12 mutation. In the proposed study, the investigators plan to knock out Septin14 in the mouse. SEPT14 interacts with SEPT12 and is also predominantly expressed in sperm. The mouse models and research tools could be used to explore the role of septins during spermiogenesis, to deconstruct the SEPT12 complex in the mammalian sperm, and to elucidate the functional significance of the Septin 12 mutations. Our findings may provide novel insight into the pathways human spermatogenesis, and has the potential to lead to development of therapeutic models for male infertility, and design of male contraceptives.

Conditions

Sponsors & Collaborators

  • National Cheng-Kung University Hospital

    lead OTHER

Principal Investigators

  • Pao-Lin Kuo, MD · Department of Obstetrics and Gynecology, National Cheng Kung University Hospital

Eligibility

Min Age
20 Years
Max Age
50 Years
Sex
MALE
Healthy Volunteers
Yes

Timeline & Regulatory

Start
2014-08-31
Primary Completion
2017-07-31
Completion
2017-07-31

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Read the full study record

This page highlights key information. For complete eligibility criteria, study locations, investigator contacts, and the full protocol, visit the original record on ClinicalTrials.gov.

View NCT04159402 on ClinicalTrials.gov