Here we describe the AP2-Cre (“Creface”) mouse [15] as an insertion mutation in Hhat. HhatCreface/Creface embryos exhibit holoprosencephaly; extensive apoptosis in the craniofacial mesenchyme; frontonasal, mediolateral, maxillary and mandibular prominence hypoplasia; patterning defects in the facial prominences and cranial ganglia; and diminished chondrogenesis and osteogenesis. The gene discussed is HHAT; the disease is holoprosencephaly.