Iowa will need to complete its quest for a perfect regular season without its leading rusher.
Redshirt freshman running back Adam Robinson likely will miss the rest of the regular season after suffering a high left ankle sprain in Saturday's win against Michigan State.
Robinson has started the past seven games for Iowa (No. 4 BCS, No. 7 AP) and ranks fourth in the Big Ten in rushing (78.6 ypg).
He registered career highs in both attempts (27) and rushing yards (109) against the Spartans.
The loss of Robinson, who has rushed for 629 yards and five touchdowns this season, shrinks what's already a slim margin of error for the Hawkeyes, who rank 86th in the nation in scoring offense.
"There's a chance we could get him back," Ferentz said, "but a running back with a bad ankle, it's not a good thing."
Ferentz likened Robinson's injury to the one that kept tight end Tony Moeaki out for several games this year.
True freshman Brandon Wegher will make his first career start Saturday against Indiana (ESPN, noon ET). Wegher has rushed for 321 yards and three touchdowns on 87 carries.
The Hawkeyes lost sophomore running back Jewel Hampton, the projected starter entering the season, to a knee injury in preseason camp.
Ferentz also said starting right guard Dace Richardson will miss the rest of the regular season with a broken bone in his leg.
Adam Rittenberg covers Big Ten football for ESPN.com. He can be reached at firstname.lastname@example.org. Information from The Associated Press was used in this report.