TY - JOUR
T1 - Assessment of autism-relevant behaviors in C57BKS/J leptin receptor deficient mice
AU - Greene, Susan M.
AU - Sanchez, Yatzil R.
AU - Pathapati, Nikhita
AU - Davis, Gianna N.
AU - Gould, Georgianna G.
N1 - Publisher Copyright:
© 2021 The Authors
PY - 2021/3
Y1 - 2021/3
N2 - 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-Dock7m +/+ Leprdb/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.
AB - 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-Dock7m +/+ Leprdb/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.
KW - Blood glucose
KW - Cognitive flexibility
KW - Corticosteroid
KW - Gestational diabetes
KW - Leptin receptor
KW - Social dominance
KW - Social preferences
UR - http://www.scopus.com/inward/record.url?scp=85100218160&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85100218160&partnerID=8YFLogxK
U2 - 10.1016/j.yhbeh.2020.104919
DO - 10.1016/j.yhbeh.2020.104919
M3 - Article
C2 - 33428921
AN - SCOPUS:85100218160
SN - 0018-506X
VL - 129
JO - Hormones and Behavior
JF - Hormones and Behavior
M1 - 104919
ER -