The team started with IKK2 because IKK1 hadn't been cloned yet (it has since been1). "The question was, 'What is the role of each one of those kinases and what other roles might they play?'... not that we anticipated them to be that different," recalls Verma. In fact, they turned out to be very different.
The team created IKK2 knockout mice. They found that between days 12-13 and 13-14 of the gestation period, the animals died of liver apoptosis, probably due to tumor necrosis factor aTNFa. Although the researchers could detect weak normal IKK1 activity, the results made it clear that IKK1 could not make up for the absence of IKK2. In subsequent studies, the team made IKK1 knockouts and found that the animals survived gestation, but their limbs never extended and the animals died soon after birth.2,3 Double knockouts died at day 9-12 of the gestation period, and the ...
