PMID:15509788

Citation	Martins, LM, Morrison, A, Klupsch, K, Fedele, V, Moisoi, N, Teismann, P, Abuin, A, Grau, E, Geppert, M, Livi, GP, Creasy, CL, Martin, A, Hargreaves, I, Heales, SJ, Okada, H, Brandner, S, Schulz, JB, Mak, T and Downward, J (2004) Neuroprotective role of the Reaper-related serine protease HtrA2/Omi revealed by targeted deletion in mice. Mol. Cell. Biol. 24:9848-62
Abstract	The serine protease HtrA2/Omi is released from the mitochondrial intermembrane space following apoptotic stimuli. Once in the cytosol, HtrA2/Omi has been implicated in promoting cell death by binding to inhibitor of apoptosis proteins (IAPs) via its amino-terminal Reaper-related motif, thus inducing caspase activity, and also in mediating caspase-independent death through its own protease activity. We report here the phenotype of mice entirely lacking expression of HtrA2/Omi due to targeted deletion of its gene, Prss25. These animals, or cells derived from them, show no evidence of reduced rates of cell death but on the contrary suffer loss of a population of neurons in the striatum, resulting in a neurodegenerative disorder with a parkinsonian phenotype that leads to death of the mice around 30 days after birth. The phenotype of these mice suggests that it is the protease function of this protein and not its IAP binding motif that is critical. This conclusion is reinforced by the finding that simultaneous deletion of the other major IAP binding protein, Smac/DIABLO, does not obviously alter the phenotype of HtrA2/Omi knockout mice or cells derived from them. Mammalian HtrA2/Omi is therefore likely to function in vivo in a manner similar to that of its bacterial homologues DegS and DegP, which are involved in protection against cell stress, and not like the proapoptotic Reaper family proteins in Drosophila melanogaster.
Links	PubMed PMC525490 Online version:10.1128/MCB.24.22.9848-9862.2004
Keywords	Animals; Apoptosis/physiology; Base Sequence; Carrier Proteins/genetics; Carrier Proteins/physiology; Corpus Striatum/abnormalities; Corpus Striatum/embryology; Corpus Striatum/enzymology; DNA/genetics; Female; Gene Targeting; Male; Mice; Mice, Inbred C57BL; Mice, Knockout; Mitochondria/metabolism; Mitochondrial Proteins/deficiency; Mitochondrial Proteins/genetics; Mitochondrial Proteins/physiology; Neurons/pathology; Parkinsonian Disorders/embryology; Parkinsonian Disorders/etiology; Parkinsonian Disorders/genetics; Phenotype; Pregnancy; Proteins/metabolism; Serine Endopeptidases/deficiency; Serine Endopeptidases/genetics; Serine Endopeptidases/physiology; X-Linked Inhibitor of Apoptosis Protein
edit table

Annotations

Gene product	Qualifier	GO ID	GO term name	Evidence Code	with/from	Aspect	Notes	Status
edit table

References

See Help:References for how to manage references in GONUTS.