Transgenic mice with neuron-specific overexpression of HtrA2/Omi suggest a neuroprotective role for HtrA2/Omi.
Mammalian serine protease HtrA2/Omi has been known as an apoptosis inducer involved inactivation of caspase-dependent as well as caspase-independent cell death. Recent studies with the HtrA2/Omi mutant and knockout mouse models, however, suggested that HtrA2/Omi might play a protective role in neurons. It is important to establish a transgenic mouse model with neuron-specific overexpression of HtrA2/Omi to clarify the physiological function of mammalian HtrA2/Omi in neurons. In the present study, a transgene containing HtrA2/Omi cDNA downstream of a rat neuron-specific enolase promoter was constructed and microinjected into the pronuclei of fertilized zygotes to establish transgenic mice. Transgenic mice successfully overexpressed HtrA2/Omi in brain tissue. As expected, HtrA2/Omi-overexpressing transgenic mice showed normal development without any sign of apoptotic cell death. Our results suggest that the primary function of neuronal HtrA2/Omi might be to protect neurons against stress in contrast to its role in the somatic system.
Liu
Ming-Jie
MJ
Laboratory of Genetics, Department of Microbiology and Immunology, Institute for Medical Science, Chonbuk National University Medical School, Chonju, Chonbuk 561-756, South Korea.
Liu
Meng-Lu
ML
Shen
Yan-Fei
YF
Kim
Jin-Man
JM
Lee
Byung-Ho
BH
Lee
Youn-Sik
YS
Hong
Seong-Tshool
ST
D000818:Animals; D017209:Apoptosis / Q000235:genetics; D015153:Blotting, Western; D001921:Brain / Q000378:metabolism; D002460:Cell Line; D002478:Cells, Cultured; D005260:Female; D015870:Gene Expression; D000074923:High-Temperature Requirement A Serine Peptidase 2; D006801:Humans; D007668:Kidney / Q000378:metabolism; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D024101:Mitochondrial Proteins / Q000235:genetics / Q000378:metabolism*; D009474:Neurons / Q000378:metabolism*; D018696:Neuroprotective Agents / Q000378:metabolism*; D010751:Phosphopyruvate Hydratase / Q000235:genetics; D010957:Plasmids / Q000235:genetics; D016133:Polymerase Chain Reaction; D011401:Promoter Regions, Genetic / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D012098:Reproduction / Q000235:genetics; D012697:Serine Endopeptidases / Q000235:genetics / Q000378:metabolism*; D013997:Time Factors; D014162:Transfection
D024101:Mitochondrial Proteins; D018696:Neuroprotective Agents; D012697:Serine Endopeptidases; C000615914:HTRA2 protein, human; D000074923:High-Temperature Requirement A Serine Peptidase 2; C000615915:Htra2 protein, mouse; D010751:Phosphopyruvate Hydratase