Gestational diabetes mellitus (GDM) was associated with greater autism risk in epidemiological studies. Disrupted leptin signaling may contribute to their coincidence, as it is found in both disorders. Given this we examined leptin receptor (Lepr) deficient (BKS.Cg-Dock7^m +/+ Lepr^db/J diabetic (db)) heterozygous (db/+) mice for autism-relevant behaviors. BKS db/+ females are lean with normal blood glucose, but they develop GDM while pregnant. We hypothesized BKS db/+ offspring might exhibit physiological and behavior traits consistent with autism. Adolescent body weight, fasting blood glucose, serum corticosterone, social preferences, self-grooming, marble burying, social dominance and cognitive flexibility of BKS db/+ mice was compared to C57BLKS/J (BKS) and C57BL/6J (BL6) mice. Male db/+ weighed more and had higher blood glucose and corticosterone relative to BL6, but not BKS mice. Also, male db/+ lacked social interaction preference, explored arenas less, and buried more marbles than BL6, but not BKS males. Male and female db/+ were more dominant and made more mistakes in water T-mazes locating a sunken platform after its position was reversed than BL6, but not BKS mice. Overall BKS db/+, particularly males, exhibited some autism-like social deficits and restrictive-repetitive behaviors relative to BL6, but BKS strain contributions to BKS db/+ behaviors were evident. Since BKS db/+ and BKS behavioral and physiological phenotypes are already so similar, it will be difficult to use these models in studies designed to detect contributions of fetal GDM exposures to offspring behaviors.

在流行病学研究中，妊娠期糖尿病（GDM）与更大的自闭症风险相关。中断的瘦素信号可能导致它们的巧合，因为它在两种疾病中都存在。鉴于此，我们检查了瘦素受体 (Lepr) 缺陷 (BKS.Cg-Dock7 ^m +/+ Lepr ^db/J 糖尿病 (db)) 杂合子 (db/+) 小鼠用于自闭症相关行为。BKS db/+ 雌性较瘦，血糖正常，但她们在怀孕期间会患上 GDM。我们假设 BKS db/+ 后代可能表现出与自闭症一致的生理和行为特征。将 BKS db/+ 小鼠与 C57BLKS/J (BKS) 和 C57BL/6J (BL6) 小鼠的青少年体重、空腹血糖、血清皮质酮、社会偏好、自我修饰、大理石掩埋、社会优势和认知灵活性进行了比较。与 BL6 相比，雄性 db/+ 体重更重，血糖和皮质酮更高，但 BKS 小鼠则不然。此外，与 BL6 相比，男性 db/+ 缺乏社交偏好，探索竞技场更少，埋藏的弹珠更多，但 BKS 男性则不然。雄性和雌性 db/+ 比 BL6 小鼠更占优势，并且在定位凹陷平台后的水 T 迷宫中比 BL6 小鼠犯更多错误，但不是 BKS 小鼠。总体而言，BKS db/+，尤其是男性，表现出与 BL6 相关的一些类似自闭症的社交缺陷和限制性重复行为，但 BKS 应变对 BKS db/+ 行为的贡献是显而易见的。由于 BKS db/+ 和 BKS 行为和生理表型已经非常相似，因此很难在旨在检测胎儿 GDM 暴露对后代行为的贡献的研究中使用这些模型。