a NPY analysis in CPE-E342Q mouse hypothalamus. Protein was extracted from WT and CPE-E342Q (n = 3 each) mouse hypothalamic extracts and NPY was measured using a mature NPY specific EIA kit. WT and CPE-E342Q (n = 3 each) hypothalamic tissue extracts were also separated on reverse phase HPLC column and fractions corresponding to NPY standard were analyzed by the NPY EIA kit. Bar graphs show collective result for both total and HPLC analyzed tissue samples (n = 6 mice). Note the 71.85% decrease in the level of mature NPY peptide in CPE-E342Q compared to WT mice, Mann Whitney’s non-parametric test, +p = 0.0152, values are mean ± SEM. b Bar graphs show proinsulin in CPE-E342Q mice at 12 weeks of age was significantly increased in comparison with WT mice (WT = 26.9 ± 1.008 pmol/L, CPE-E342Q = 79.48 ± 2.94 pmol/L), Student’s t test, +p < 0.0001 for CPE-E342Q mice compared with WT. The values are the mean ± SEM, n = 5 mice per group. c Bar graphs show insulin in CPE-E342Q mice at 12 weeks of age was significantly decreased in comparison with WT mice (WT = 1.223 ± 0.03 ng/ml, CPE-E342Q = 0.269 ± 0.017 ng/ml). Student’s t test, +p < 0.0001 for CPE-E342Q mice compared with WT. The values are the mean ± SEM, n = 5 mice per group. d Bar graphs show fasting glucose levels were significantly higher in CPE-KO and CPE-E342Q mice in comparison with WT mice. One-way ANOVA analysis followed by Tukey’s post hoc multiple comparison test, [F(2,45)=92.62, p < 0.0001]. +p < 0.0001 for both CPE-E342Q and CPE-KO mice compared with WT. The values are the mean ± SEM, n = 12 for CPE-KO, n = 12 for CPE-E342Q, n = 24 for WT. e Body weight of CPE-KO, CPE-E342Q, and WT mice. Weights of male and female WT, CPE-KO, CPE-E342Q mice were recorded from 5 to 14 week of age. The values are the mean ± SEM, n = 12 for CPE-KO, n = 12 for CPE-E342Q, n = 24 for WT. f Photograph showing the size of CPE-E342Q, WT and CPE-KO mice at 32 weeks of age. Note the obesity of CPE-E342Q and CPE-KO mice. g Fertility evaluation of CPE-E342Q mice compared with WT. Table shows CPE-E342Q homozygote mice are infertile. Hom = homozygote, Het = heterozygote, Wt = wild type. Mice were 6–9-week old.