The Al-Nuri mosque and its iconic leaning minaret were leveled on Wednesday evening as US-backed Iraqi forces closed in on militant hold-outs in the northern city.
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State Department spokeswoman Heather Nauert said the bombing of such a site "only further proves that ISIS has no respect for Iraq's identity, culture or its religions."
Islamic State leader Abu Bakr al-Baghdadi once exploited the powerful symbolism of the mosque to boost his stature when he gave his first sermon as leader of the group. But his fighters apparently preferred to demolish the shrine - and attempt to blame US air strikes - rather than allow it to fall into the hands of advancing government forces.
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"The despicable act is a crime not only against the people of Mosul and Iraq, but the world," Nauert said. "The world has yet again lost an important part of our shared heritage at the hands of ISIS."
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