Figure 1.

Hematopoietic-specific expression of mutant JAK2–induced adipose tissue atrophy, severe hypoglycemia, and global metabolic changes in MPN mice. (A) Representative pictures of wild-type (WT) and VF- and E12-mutant mice at 2 to 4 months after induction with tamoxifen. Red and blue asterisks indicate reduced subcutaneous and epididymal white adipose tissue (eWAT), respectively. (B) Body weight at 2 to 4 months after induction with tamoxifen (n = 8-12 mice per genotype). (C) eWAT weight (n = 8-12 mice per genotype). (D) Ratios of lean body mass/total body mass (solid colors) and fat mass/total body mass (transparent colors) at 2 to 4 months after induction with tamoxifen (n = 4-5 mice per group). (E-F) Food intake (E) and locomotor activity (on x-, y-, and z-axes) (F) as measured by comprehensive laboratory animal monitoring system (n = 5 mice per genotype). (G) Nonfasting blood glucose levels at 12 (VF) and 6 weeks (E12) after tamoxifen induction (n = 5-6 mice per genotype). (H) Serum insulin levels at 12 (VF) and 6 weeks (E12) after tamoxifen induction (n = 5-6 and n = 8 mice per genotype, respectively). (I,J) Nonfasting blood glucose levels (I) and time course of change in body weight (J) after tamoxifen induction (n = 5 mice per genotype). (K) Glucose tolerance test (GTT) 6 hours after starvation at 12 (VF) and 6 weeks (E12) after tamoxifen induction (n = 10-12 mice per genotype). (L) Tamoxifen-induced mice were treated with ruxolitinib (90 mg/kg twice daily). Time course of fasting blood glucose levels, peripheral hemoglobin levels, and reticulocyte counts (n = 5-6 mice per genotype). (M) GTT in recipients transplanted with BM cells (2 × 10⁶) from WT, VF, or E12 donor mice (n = 6 mice per genotype). All data are presented as mean ± standard error of the mean. One- or 2-way analyses of variance followed by Tukey’s multiple comparison tests were used for multiple-group comparisons. *P < .05, **P < .01, ***P < .001.