Figure 1.
Demonstration and validation of Cre-excision.
(A) GFP staining of hypothalamic sections from crossbred LepR-cre mice×ROSA-eYFP mice illustrates the cre-excision pattern in the hypothalamus, a’f’ represents rostral (bregma −1) to caudal (bregma −2.5) [51] hypothalamic sections, scale bar = 500 µm. (B) PCR analysis confirmed successful excision of human mutant htt exon1 in leptin receptor-expressing neurons in the hypothalamus, but not in a region (striatum), which lacks leptin receptor-expressing neurons.
Figure 2.
Body weight in BACHD×LepR-cre offspring.
Body weight at 2- and 6-months in males and females from the two different breedings between BACHD and BACHD/LepR-cre (n = 4–10/genotype/sex/breeding). Both BACHD and BACHD/LepR-cre developed early onset obesity but no significant differences between BACHD and BACHD/LepR-cre could be detected in any of the breedings or sexes. (A) F BACHD×M LepR-cre, females, (B) F BACHD×M LepR-cre, males, (C) F LepR-cre×M BACHD, females, and (D) F LepR-cre×M BACHD, males. All data are expressed as means ± SEM. Significant differences from WT and/or LepR-cre mice: * p<0.05 (see Statistical Results S1).
Figure 3.
Body composition in BACHD×LepR-cre offspring.
The graphs show percentage body fat as assessed with dual energy x-ray absorptiometry (DEXA) at 6-months in males and females from the two different breedings (n = 4–10/genotype/sex/breeding). Both BACHD and BACHD/LepR-cre showed increased percentage of body fat but there were no significant differences between BACHD and BACHD/LepR-cre in the two breedings and sexes. (A) F BACHD×M LepR-cre, females, (B) F BACHD×M LepR-cre, males, (C) F LepR-cre×M BACHD, females, and (D) F LepR-cre×M BACHD, males. All data are expressed as means ± SEM. Significant differences from WT and/or LepR-cre mice: * p<0.05 (see Statistical Results S1).
Figure 4.
Endocrine measurements in BACHD×LepR-cre offspring.
Circulating levels of leptin and insulin were measured in 6-month old female mice from the second breeding (n = 9–10/genotype). (A) Both BACHD and BACHD/LepR-cre showed elevated leptin levels but no significant differences between BACHD and BACHD/LepR-cre could be detected. (B) Only BACHD mice displayed significantly higher insulin levels than wt mice. However, no significant differences could be detected between BACHD and BACHD/LepR-cre. All data are expressed as means ± SEM. Significant differences from WT and/or LepR-cre mice: * p<0.05 (see Statistical Results S1).
Figure 5.
Assessment of anxiety-like behavior in BACHD×LepR-cre offspring.
Both BACHD and BACHD/LepR-Cre displayed anxiety-like behavior at 6 months of age, with reduced time spent on open arms (A) as well as reduced number of entries onto the open arms (B) in the EPM at 6-months (n = 4–10/genotype/sex/breeding). However, no difference could be detected between BACHD and BACHD/LepR-cre mice. All data are expressed as means ± SEM. Significant differences from WT and LepR-cre mice: * p<0.05 (see Statistical Results S1).
Figure 6.
Assessment of depressive-like behavior in BACHD×LepR-cre offspring.
No differences in immobility could be detected in the FST between any of the genotypes in the breeding between F BACHD and M LepR-cre (A). For the F LepR-cre×M BACHD breeding (B), LepR-cre mice spent significantly more time immobile than WT and LepR-cre mice. (n = 4–10/genotype/sex/breeding). All data are expressed as means ± SEM. significant differences from WT and LepR-cre mice: * p<0.05 (see Statistical Results S1).