Journal of the Endocrine Society
Oxford University Press
image
SUN-100 Mice Lacking Paternally Expressed DLK1 Reach Puberty at a Lower Body Weight Than Littermate Controls
Volume: 4, Issue: Suppl 1
DOI 10.1210/jendso/bvaa046.1567

Highlights

Notes

Abstract

Body fat content along with a variety of genetic, environmental and psychosocial factors are responsible for the development and maintenance of reproductive function, especially in females. Epidemiologic studies indicate a relationship between increased body mass index and earlier puberty in girls. In contrast, a significant delay in puberty and menarche is seen in girls who are very physically active and have markedly diminished body fat. This link between reproduction and metabolism was reinforced with the recent report of loss-of-function mutations in the Delta-like homolog 1 (DLK1) gene in girls with central precocious puberty (CPP) and increased body fat. DLK1 is a paternally expressed gene located on chromosome 14q32.2 in a locus associated with Temple syndrome (TS), an imprinting disorder caused mainly by maternal parental disomy (mUPD). Dlk1 knockout mice display pre- and postnatal growth retardation, a phenotype that overlaps with human mUPD14. However, precocious puberty, a common finding associated with TS, was not carefully characterized in these mice. We used a Dlk1 deficient mouse model to determine the effects of Dlk1 on pubertal maturation. We confirmed by RT-qPCR that Dlk1 mRNA was undetectable in the mediobasal hypothalamus, where kisspeptin and other regulators of puberty are expressed, of Dlk+/p- mice (which inherited the mutant allele from their father) whereas it was present in Dlk+/+ mice. As reported previously, body weight was significantly lower in juvenile male and female Dlk+/p- mice, compared to wild-type littermate controls. Interestingly, mutant and control female mice achieved vaginal opening, a marker of puberty onset, at a similar age (Dlk+/p-: 29.8 ± 1.5 days, n=11 vs. Dlk+/+: 29.1 ± 0.7 days, n=15, p=0.6) despite a considerably lower body weight in the Dlk1 deficient mice at the time of vaginal opening (Dlk+/p-: 10.1 ± 0.8 g vs. Dlk+/+: 14.3 ± 0.3 g, p<0.0001). Similarly, in the Dlk+/p- males, preputial separation occurred at a lower body weight than in controls (Dlk+/p-: 12.4 ± 0.3 g, n=9 vs. Dlk+/+: 14.1 ± 0.2 g, n=19, p<0.0001). We hypothesize that the lack of Dlk1 at the hypothalamic level may be attenuating the effect of the low body weight on determining pubertal onset. These findings suggest that DLK1 is an important link between body weight and pubertal development in mice, as has been shown in humans.

Macedo, Abreu, Tellez, Naule, Kim, Capo-Battaglia, Song, Roberts, Latronico, Carroll, and Kaiser: SUN-100 Mice Lacking Paternally Expressed DLK1 Reach Puberty at a Lower Body Weight Than Littermate Controls
https://www.researchpad.co/tools/openurl?pubtype=article&doi=10.1210/jendso/bvaa046.1567&title=SUN-100 Mice Lacking Paternally Expressed DLK1 Reach Puberty at a Lower Body Weight Than Littermate Controls&author=Delanie B Macedo,Ana Paula Abreu,Silvia L Tellez,Lydie Naule,Han Kyeol Kim,Athena Capo-Battaglia,Yong Bhum Song,Stephanie Roberts,Ana Claudia Latronico,Rona Stephanie Carroll,Ursula B Kaiser,&keyword=&subject=Pediatric Endocrinology,Pediatric Sexual Differentiation, Puberty, and Bone Biology,AcademicSubjects/MED00250,