Murine Ovarian Development Is Not Affected by Inactivation of the Bcl-2 Family Member Diva

Department of Genetics, St. Jude Children's Research Hospital, Memphis, Tennessee 38105, USA.
Molecular and Cellular Biology (Impact Factor: 4.78). 11/2002; 22(19):6866-70. DOI: 10.1128/MCB.22.19.6866-6870.2002
Source: PubMed


Diva (also called Boo/Bcl-B) is a member of the Bcl-2 gene family and most likely functions during apoptosis. Diva is highly
expressed in the ovary, and both pro- and antiapoptotic functions have been ascribed to this protein. To determine the role
of Diva during murine development, we used gene targeting to inactivate Diva. The Diva-null mice are born at the expected ratios, are fertile, and have no obvious histological abnormalities, and long-term
survival did not differ from littermate controls. Additionally, Diva was not required for apoptosis occurring from genotoxic
insult in the ovaries or other organs. Thus, Diva is not critical for the normal development of the ovaries, or in its absence
its function is subserved by another protein.

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    • "At the moment, at least two observations support this latter possibility. First, BCL2L10 knockout mice demonstrated no overt phenotype at the whole animal level (Russell et al., 2002). Secondly, BCL2L10 exhibits particularly high evolutionary rates in mice and rats (Aouacheria et al., 2005; Guillemin et al., 2009, 2011). "
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    ABSTRACT: STUDY QUESTION What is the expression status and subcellular localization of the maternally expressed Bcl-2 family member, BCL2L10, in early human embryos of diverse developmental stages and quality?
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    • "Interestingly, such cell death in the developing nervous system and ovaries was not prominent in Diva null mice which displayed no growth or fertility abnormalities. Moreover under ionizing radiation, the rate of apoptosis that occurred in the ovaries of Diva null mice was no different from the wild type [36]. Similar discrepancies were noted in the small intestines of Bcl2 null mice which revealed no difference in apoptotic rates from the wild type mice after gamma radiation exposure. "
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    ABSTRACT: Diva is a member of the Bcl2 family but its function in apoptosis remains largely unclear because of its specific expression found within limited adult tissues. Previous overexpression studies done on various cell lines yielded conflicting conclusions pertaining to its apoptotic function. Here, we discovered the expression of endogenous Diva in PC12 neuronal-like cell line and rat bone marrow mesenchymal stem cells (BMSCs), leading to their utilisation for the functional study of Diva. Through usage of recombinant Fas ligand, hydrogen peroxide, overexpression and knock down experiments, we discovered that Diva plays a crucial pro-survival role via the mitochondrial death pathway. In addition, immunoprecipitation studies also noted a decrease in Diva's interaction with Bcl2 and Bax following apoptosis induced by oxidative stress. By overexpressing Diva in BMSCs, we had observed an increase in the cells' capacity to survive under oxidative stress and microglial toxicity. The result obtained from our study gives us reason to believe that Diva plays an important role in controlling the survival of BMSCs. Through overexpression of Diva, the viability of these BMSCs may be boosted under adverse conditions.
    Full-text · Article · Aug 2012 · PLoS ONE
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    • "In mice the expression of Boo/Diva appears restricted to the ovaries and to a lesser extent in the epididymis (Inohara et al., 1998; Song et al., 1999), perhaps suggestive of a critical role in reproduction. However, upon analysis, Boo/Diva-deficient mice were found to be fertile, not have any obvious developmental defects and cells derived from these animals responded normally to various apoptotic stimuli (Russell et al., 2002). This may, however, not truly reflect the role of this Bcl-2 pro-survival protein in humans, since the expression pattern of the human Boo/Diva homologue Bcl-b, differs from that of the mouse protein by being much more widely expressed. "
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    ABSTRACT: The link between evasion of apoptosis and the development of cellular hyperplasia and ultimately cancer is implicitly clear if one considers how many cells are produced each day and, hence, how many cells must die to make room for the new ones (reviewed in Raff, 1996). Furthermore, cells are frequently experiencing noxious stimuli that can cause lesions in their DNA and faults in DNA replication can occur during cellular proliferation. Such DNA damage needs to be repaired efficiently or cells with irreparable damage must be killed to prevent subsequent division of aberrant cells that may fuel tumorigenesis (reviewed in Weinberg, 2007). The detection of genetic lesions in human cancers that activate prosurvival genes or disable proapoptotic genes have provided the first evidence that defects in programmed cell death can cause cancer (Tagawa et al., 2005; Tsujimoto et al., 1984; Vaux, Cory, and Adams, 1988) and this concept was proven by studies with genetically modified mice (Egle et al., 2004b; Strasser et al., 1990a). It is therefore now widely accepted that evasion of apoptosis is a requirement for both neoplastic transformation and sustained growth of cancer cells (reviewed in Cory and Adams, 2002; Hanahan and Weinberg, 2000; Weinberg, 2007). Importantly, apoptosis is also a major contributor to anticancer therapy-induced killing of tumor cells (reviewed in Cory and Adams, 2002; Cragg et al., 2009). Consequently, a detailed understanding of apoptotic cell death will help to better comprehend the complexities of tumorigenesis and should assist with the development of improved targeted therapies for cancer based on the direct activation of the apoptotic machinery (reviewed in Lessene, Czabotar, and Colman, 2008).
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