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ARS Home » Plains Area » Houston, Texas » Children's Nutrition Research Center » Research » Publications at this Location » Publication #203266
Title: Evaluation of Mecp2(R308/Y) mutant mice as a model to study fetal programming

Author
item YU, ZHIYIN - BAYLOR COLLEGE MED
item ROSETTA, REBECCA - BAYLOR COLLEGE MED
item SANGI-HAGHPEYKAR, HALEH - BAYLOR COLLEGE MED
item Van Den Veyver, Ignatia

Submitted to: Society for Gynecologic Investigation
Publication Type: Abstract Only
Publication Acceptance Date: 10/30/2006
Publication Date: 3/14/2007
Citation: Yu, Z., Rosetta, R., Sangi-Haghpeykar, H., Van Den Veyver, I. 2007. Evaluation of Mecp2(R308/Y) mutant mice as a model to study fetal programming [abstract]. Society for Gynecologic Investigation 2007 Annual Scientific Meeting. Abstract No. 950304.

Interpretive Summary:

Technical Abstract: DNA (CpG) methylation is altered at candidate loci after prenatal modification of dietary methyl donor supply. Mecp2(R308/Y) mutant mice, with a truncating mutation of the methyl-CpG-binding protein 2 gene which models Rett syndrome, have increased weight gain on a high methyl donor diet. Rett syndrome patients have subtle changes in glucose metabolism. To investigate whether Mecp2(R308/Y) mice are a sensitive model for epigenetic modification of weight and glucose tolerance (GT), we fed them three different methyl-donor diets and studied their weight and glucose tolerance. Female 129Sv/Ev Mecp2(R308/X) mice were fed diets with high (HM), regular (RM), or low (LM) methyl donor content starting 4 weeks prior to mating to wt males; offspring received the same diets. Mecp2(R308/Y) and wt male offspring were compared. Diets were continued during lactation and in offspring and were based on the Purina 5001 rodent diet; the HM diet contained 22 mg/kg folic acid, 15g/kg betaine, and was supplemented with vitamin B12 and zinc; the LM diet contained 1.3 mg/kg folic acid, without other supplements. Male offspring were weighed weekly until 12 weeks, then monthly until 1 year of age. Intraperitoneal glucose tolerance tests (GTT) and insulin tolerance tests (ITT) were performed at 6 months and 1 year (n=9-11 per group) on wt and Mecp2(R308/Y) mice. Statistical analysis was by T-test and ANOVA (significance set at p<0.05). At 6 months Mecp2(R308/Y) mice are heavier than wt mice on all diets, the effect was biggest for HM diet: HM: 28.9+/-4.7gr vs. 24.3+/-1.7gr (n=18 each), p=0.0004; LM: 25.7+/- 1.7gr vs. 23.4+/-1.8gr (n=19 and 18), p=0.0002 and RM: 25.9+/-3.5gr vs. 23.5+/-2.5gr, p=0.017 (n=19 and 21). There was no weight difference at 1 year. Mecp2(R308/Y), but not wt mice have impairment of glucose tolerance at 6 months compared to 1 year on HM (p=0.0009) and LM (p=0.004), but not on RM diet. At 6 months, Mecp2(R308/Y) mice on HM (p=0.03) and LM (p=0.007) diet had impaired GT compared to wt mice. There were no significant GTT or ITT differences at 1 year. We confirmed that 129/SvEv Mecp2(R308/Y) mice are heavier than wt mice and have diet-dependent impairment in glucose tolerance at 6 months. This suggests that these mice are a good model to study fetal programming.