Flaherty John P, Spruce Catrina A, Fairfield Heather E, Bergstrom David E
New York College of Osteopathic Medicine of New York Institute of Technology, Old Westbury, New York, USA.
Genesis. 2010 Sep;48(9):568-75. doi: 10.1002/dvg.20655.
NADPH oxidase complexes are multiprotein assemblies that generate reactive oxygen species in a variety of mammalian tissues. The canonical phagocytic oxidase consists of a heterodimeric, enzymatic core comprised of the transmembrane proteins, CYBB andCYBA and is regulated, in part, by an "organizing" function of NCF1 and an "activating" activity of NCF2. In contexts outside of the phagocyte, these regulatory functions may be encoded not only by NCF1 and NCF2, but also alternatively by their respective paralogues, NOXO1 and NOXA1. To allow tissue-specific dissection of Noxa1 function in mouse, we have generated an allele of Noxa1 suitable for conditional inactivation. Moreover, by crossing Noxa1 conditional allele carriers to B6.129S4-Meox2(tm1(Cre)Sor)/J mice, we have generated first, Noxa1-null heterozygotes, and ultimately, Noxa1-null homozygotes. Through the thoughtful use of tissue-specific, Cre-expressing mouse strains, the Noxa1 conditional allele will offer insight into the roles of NOXA1 in the variety of tissues in which it is expressed.
NADPH氧化酶复合物是多蛋白组装体,可在多种哺乳动物组织中产生活性氧。典型的吞噬氧化酶由一个异源二聚体酶核心组成,该核心由跨膜蛋白CYBB和CYBA构成,并且部分受NCF1的“组织”功能和NCF2的“激活”活性调节。在吞噬细胞之外的环境中,这些调节功能不仅可能由NCF1和NCF2编码,还可能由它们各自的旁系同源物NOXO1和NOXA1编码。为了在小鼠中对Noxa1功能进行组织特异性剖析,我们构建了一个适合条件性失活的Noxa1等位基因。此外,通过将携带Noxa1条件等位基因的小鼠与B6.129S4-Meox2(tm1(Cre)Sor)/J小鼠杂交,我们首先获得了Noxa1基因敲除杂合子,最终获得了Noxa1基因敲除纯合子。通过精心使用组织特异性表达Cre的小鼠品系,Noxa1条件等位基因将有助于深入了解NOXA1在其表达的多种组织中的作用。