The 22/45 has a grip design of a shape more like a 1911. The other MK series guns use Bill's original grip design. The Government Target model has more of a bull barrel,, while the Target model has a tapered barrel. The 22/45 uses different magazines than the original design,, due to the angle differences.
You can go online to Ruger's website & look at the MKIV's in the same models,, and see the differences.