Lethal phenotype of mice carrying aSept11null mutation

Abstract

Septins are cytoskeletal GTP-binding proteins involved in processes characterized by active membrane movement, such as cytokinesis, vesicle trafficking and exocytosis. Most septins are expressed ubiquitously, however, some septins accumulate in particular tissues. The ubiquitous SEPT11 also shows high expression levels in the central nervous system and in platelets. Here, SEPT11 is involved in vesicle trafficking and may play a role in synaptic connectivity. Interestingly, mice that harbor a homozygous Sept11 null mutation, die in utero. From day 11.5 post coitum onwards, development of homozygous embryos seems to be retarded and the embryos from day 13.5 onwards were dead.

Genetic Deletion of SEPT7 Reveals a Cell Type-Specific Role of Septins in Microtubule Destabilization for the Completion of Cytokinesis

“…Sept7 −/− (KO) embryos were found in utero up to embryonic day 6.5 (E6.5)-E7.0, but not after E10.5, indicating early embryonic lethality (Figure 1B). As the genetic loss of SEPT9 or SEPT11 causes embryonic death by E10 [21] and E13 [22] respectively, SEPT7 appears no less vital than these major subunits. These data obviously indicate that septins are dispensable for the majority of cells to execute mitosis in early mouse embryo.…”

Septin functions in organ system physiology and pathology

“…Sept7 −/− mice were never born, arresting early in development possibly due to mitotic failure (Kinoshita, 2008). Development of Sept11 −/− mice ceased at day 11.5 in utero and the mice died by day 13.5 (Roseler et al, 2011). Despite the development of a healthy yolk sac, heartbeat, and blood vessels, Sept9 −/− embryos died by day 10 of gestation, exhibiting mesenchymal tissue degeneration and extensive cell death (Fuchtbauer et al, 2011).…”

Highlight on septins

“…This finding is also partly supported by a two-hybrid study on the interaction between septin group members by Sandrock et al (2011). Septin genomics are discussed in the review by Russell and Hall (2011) and the effect of knocking out different septins genes is discussed in the articles by Füchtbauer et al (2011) and Röseler et al (2011) with the surprising results that some septins are essential and their deletion leads to lethality, whereas others show none or only mild phenotypes. The expression pattern of most mammalian septins is very complex with many splice variants being expressed/reported.…”