Dissect Assembly Rules of SPET12 Complex in the Mammalian Sperm
Condition: Spermatozoa; Fertility
Study type: Observational

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.
    

Detailed 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.
    

Observational model: Case-Control
Time perspective: Prospective
Sampling method: Probability Sample
Study population: 
        The participants were clinically diagnosed by semen analysis and further collected the
        normal human sperm.
      
Biospecimen description: 
      Sperm