Figure 1.

Generation of Pomc^tm1/tm1 mice that develop the characteristic melanocortin obese phenotype. A, Schematic of targeted Pomc allele for knock-in of QKQR mutation into Pomc exon 3 with resulting impact on pre-POMC processing and ACTH_1-13 production. B, Amino acid sequence alignments for native and mutant ACTH_1-39 molecule. C, MALDI imaging MS shows ACTH_1-13 is successfully deleted from Pomc^tm1/tm1 mouse pituitary. Mass-to-charge (m/z) signals that delineate the pars distalis (PD, m/z 835 in blue represents phospholipid) and posterior lobe (P, m/z 1086 in red represents vasopressin) are shown. In addition, diacetyl-α-MSH (m/z 1706 in green) is detected in the pars intermedia (PI) of Pomc^wt/wt but not Pomc^tm1/tm1 tissue. Scale bars = 500 μM. D and G, Body weights of mice fed a regular-chow diet from weaning. Significant difference determined using two-way repeated-measures ANOVA and Bonferroni post-hoc test between Pomc^wt/wt and Pomc^tm1/tm1. *, p < 0.05; **, p < 0.01; ***, p < 0.001 or using paired Student ‘t’ test between Pomc^wt/wt and Pomc^tm1/tm1; male ^#, p < 0.05; female ^##, p < 0.01. E and H, Body length measured at 27–30 weeks for mice fed a regular-chow diet from weaning. Data are shown as mean ± SEM. Significant differences determined using one-way ANOVA and Tukey's post-hoc test. *, p < 0.05; **, p < 0.01. F and I, Percent body fat calculated from 6 MRI Dixon images/mouse. Data are shown as mean ± SEM for mice aged 26–29 weeks and fed a regular-chow diet. Significant differences determined using one-way ANOVA and Tukey's post-hoc test. ***, p < 0.001; ****, p < 0.0001.