Leo says most of his trouble will be with Windows Genuine Advantage, which will think he's installing it on a new computer. He'll have to call Microsoft and let them know he's changed the motherboard. He should also make sure he gets all the drivers he needs before he installs the new motherboard. Then he will install them immediately after booting into safe mode in Windows.
There are two problems with this. First, despite the fact that the computer may be similar to the old one, it's not identical. Drivers are different, so some things may not work. Leo recommends starting in safe mode first, and remove drivers for devices that had changed, then let Windows plug and play new drivers.
Microsoft would say no. The problem is because of Windows Genuine Advantage and the measures Microsoft takes to prevent piracy. If he gets a TechNet membership for $249 a year, he can use Windows on as many PCs as he wants.
No, he shouldn't have to. Generally in these situations, if he were to call Microsoft and tell them that he needs to replace the motherboard and needs his OEM (Original Equipment Manufacturer) version of Windows unlocked, they would do it. Leo says Microsoft's "genuine advantage" has so many false positives (meaning that Windows tells the user their copy is pirated even though it isn't), that Microsoft deals with this on a regular basis.