A 121kb deletion in chromosome 7 (Chr7) eliminating the genes Nfatc2ip, CD19, Rabep2, ATP2a1, Sh2b1, Tufm and Atxn2l was identified in a patient with Type 2 Diabetes (T2D) heterozygous for the allele. To study the role of this locus in T2D, we generated a transgenic mouse model heterozygous for the Chr7 121kb locus flanked by LoxP sites (121kbfl/+). Pancreatic β-cell specific deletion of the locus was achieved by crossing the mice to Rat insulin promoter (Rip) Cre recombinase (Cre) mouse line. Intraperitoneal glucose tolerance test (IP-GTT) was performed on 16h-fasted mice, and glucose was measured over time. Blood was collected at early timepoints to measure β-cell insulin secretion during the GTT. Differences in islet morphology were assessed in pancreas FFPE sections by immunofluorescence staining for islet endocrine hormones insulin, glucagon and somatostatin. Glucose egress during the GTT is significantly greater and plasma insulin is decreased (p<0.05) in 121kbfl/+;RipCre+. There were no overt differences in islet morphology. Our findings indicate that deletion of the locus results in a β-cell specific defect in insulin secretion, highlighting the allele’s role in conferring T2D risk in humans.