The small co-chaperone p23 overexpressing transgenic mouse

Area of Science:

• Cellular Biology
• Neuroscience
• Molecular Biology

Background:

• Endoplasmic reticulum (ER) stress is implicated in neurodegenerative diseases.
• The co-chaperone protein p23 has been identified as a modulator of ER stress-induced cell death.
• p23 is proteolytically cleaved by caspases at D142 during ER stress, generating a p19 product.

Purpose of the Study:

• To investigate the potential of uncleavable p23 (p23D142N) in mitigating neurodegenerative disease phenotypes.
• To generate and characterize transgenic mouse models overexpressing wild-type p23 or p23D142N.
• To facilitate the study of p23's role in cellular stress-induced apoptosis.

Main Methods:

• Generation of transgenic mouse lines using the ROSA promoter.
• Overexpression of wild-type p23 and a mutated, uncleavable form (p23D142N).
• Utilizing these mouse models to study ER stress and cell death pathways.

Main Results:

• Successful generation of transgenic mouse lines overexpressing p23 and p23D142N.
• The uncleavable p23 mutant (p23D142N) was designed based on blocking caspase cleavage at D142.
• These models provide a platform for in vivo studies of p23's function in ER stress.

Conclusions:

• Uncleavable p23 (p23D142N) is a promising candidate for therapeutic intervention in neurodegenerative diseases.
• The developed transgenic mice are valuable tools for exploring the role of p23 in cellular stress responses.
• Further research using these models will elucidate the mechanisms of p23 in preventing ER stress-mediated cell death.