Using heterozygous littermate controls, side-by-side comparisons demonstrated proinsulin (and insulin) deficiency (Figure 2A, lane 3, quantitation in Figure 2, C and D), which worsened upon development of diabetes in β-Hrd1–KO mice (Figure 2E), although rarely (using a preweaning β-Hrd1–KO animal) islet proinsulin (and insulin) levels appeared similar to those of control animals (e.g., Figure 2B, lanes 5 and 8). The gene discussed is INS; the disease is diabetes mellitus.