Generation and Phenotype of BAX Knockout Mice

BAX (Bcl-2 associated X protein) is a pro-apoptotic member of the Bcl-2 family and plays a crucial role in regulating programmed cell death or apoptosis. BAX, together with other apoptotic regulators such as BAK, initiates mitochondrial membrane permeabilization, releases cytochrome c and triggers apoptosis. BAX knockout mice are valuable models for studying apoptosis, neurodegeneration, immune regulation and cancer because they lack functional BAX protein and exhibit reduced apoptotic responses in various tissues.

Generation of BAX knockout mice:

BAX knockout mice are generated using homologous recombination to delete the BAX gene in embryonic stem cells, which are then implanted into mouse embryos to generate knockout offspring. By eliminating BAX, researchers disrupt the intrinsic apoptotic pathway, providing a model for studying the effects of impaired apoptosis on development and disease. In some studies, researchers have used conditional knockout strategies to delete BAX in specific tissues to explore the function of BAX in target areas such as the nervous system or immune system.

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Phenotypes of BAX knockout mice:

(1) Reduced apoptosis: BAX knockout mice exhibit significantly reduced apoptosis in various tissues, particularly in neurons and immune cells. This reduced apoptosis results in increased cell lifespan as cells that would normally be eliminated by programmed cell death remain, particularly during development and cellular stress.

(2) Nervous system effects: Loss of BAX in the nervous system results in an accumulation of neurons as the normal pruning of excess neurons during development is impaired. This accumulation is associated with alterations in brain size and structure and is often used to study neurodevelopmental and neurodegenerative diseases.

(3) Fertility issues: Male BAX knockout mice exhibit defects in germ cell apoptosis, resulting in increased spermatogonia and abnormal spermatogenesis, leading to impaired fertility. This phenotype is useful for studying the role of apoptosis in reproductive biology.

(4) Cancer susceptibility: Given its role in regulating cell death, loss of BAX results in increased resistance of certain cell types to apoptosis, leading to tumorigenesis and providing a model for studying cancer pathways marked by evasion of apoptosis.

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In summary, BAX knockout mice are essential for understanding the role of apoptosis in development, neurobiology, reproduction, and cancer, providing insights into conditions in which apoptosis regulation is disrupted.

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References

[1] Ruili Li et al., Sex Dev 2020 (https://doi.org/10.1159/000508567)

[2] Osamu Takeuchi et al., PNAS 2005 (www.pnas.orgcgi doi 10.1073pnas.0504783102)