Clinical Trial Details
— Status: Completed
Administrative data
| NCT number |
NCT04159402 |
| Other study ID # |
A-ER-102-438 |
| Secondary ID |
|
| Status |
Completed |
| Phase |
|
| First received |
|
| Last updated |
|
| Start date |
August 2014 |
| Est. completion date |
July 2017 |
Study information
| Verified date |
November 2019 |
| Source |
National Cheng-Kung University Hospital |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Observational
|
Clinical Trial 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.
Description:
Redundancy and Interchangeability of Septins Septins 3, 4, 5, 6, 11, and 12 have been knocked
out in the mouse model. Although SEPT4 abundantly expressed in different tissues, Septin4 KO
mice only shothe investigatorsd male reproductive failure. SEPT12 is exclusively expressed in
the post-meiotic germ cells, and Septin12+/- KO mice shothe investigatorsd spermatogenetic
failure. In one study, SEPT5 deficiency decreased anxiety-related behavior, increased
prepulse inhibition and delayed acquisition of rewarded goal approach, independent of mouse
genetic backgrounds. In another study, Septin3-/- and Septin5-/-mice did not show any overt
phenotypes. Knockout of a ubiquitously expressed septin, Septin6, also did not result in
abnormal phenotypes. SETP11 is ubiquitously expressed, and Sept11 null mutation died in
utero. The findings suggest redundancy and interchangeability of many septin family members.
Among the septin family members, SEPT12 and 14 may deserve special attention for the
reproductive biologists because they are mainly expressed in the testis.
