Raised late pregnancy glucose concentrations in mice carrying pups with targeted disruption of H19delta13.
OBJECTIVE
We have hypothesized that variation in imprinted growth-promoting fetal genes may affect maternal glucose concentrations in pregnancy. To test this hypothesis we evaluated the effects of fetal disruption of murine H19(Delta13) on maternal glucose concentrations in pregnancy.


METHODS
Experimental mice were pregnant females that had inherited the disrupted H19(Delta13) from their fathers and were therefore phenotypically wild type due to imprinting; approximately half of their litters were null for H19(Delta13) through maternal inheritance of the disrupted gene. In control mice approximately half the litter paternally inherited the disrupted H19(Delta13), so the pups were either genetically wild type or phenotypically wild type due to imprinting. Blood glucose concentrations were assessed by intraperitoneal glucose tolerance tests on days 1, 16, and 18 of pregnancy.


RESULTS
There were no differences in the glucose concentrations of control and experimental pregnant mice at day 1. However, at day 16 mothers carrying H19(Delta13)-null pups had a significantly higher area under the glucose tolerance test curves than controls (1,845 +/- 378 vs. 1,386 +/- 107 mmol * min * l(-1) [P = 0.01]) in association with increasing pregnancy-related insulin resistance. Although this difference lessened toward term, overall, mothers of maternally inherited H19(Delta13) mutants had significantly higher glucose concentrations during the last trimester (1,602 +/- 321 [n = 17] vs. 1,359 +/- 147 [n = 18] mmol * min * l(-1) [P = 0.009]).


CONCLUSIONS
This study provides evidence that maternal glucose concentrations in pregnant mice can be affected by targeted disruption of fetal H19(Delta13). This implies that variable fetal IGF2 expression could affect risk for gestational diabetes.
Department of Paediatrics, University of Cambridge, Cambridge, U.K. cjp1002@cam.ac.uk
Clive J
CJ
Petry
Mark L
ML
Evans
Dianne L
DL
Wingate
Ken K
KK
Ong
Wolf
W
Reik
Miguel
M
Constância
David B
DB
Dunger
D000818:Animals; D001786:Blood Glucose / Q000378:metabolism*; D016640:Diabetes, Gestational / Q000235:genetics; D005260:Female; D005333:Fetus / Q000502:physiology; D014644:Genetic Variation; D016678:Genome; D018392:Genomic Imprinting; D005951:Glucose Tolerance Test; D006943:Hyperglycemia / Q000235:genetics*; D007328:Insulin / Q000097:blood; D007335:Insulin-Like Growth Factor II / Q000378:metabolism; D008297:Male; D051379:Mice; D010375:Pedigree; D011247:Pregnancy; D011248:Pregnancy Complications / Q000235:genetics*; D062085:RNA, Long Noncoding; D022661:RNA, Untranslated / Q000235:genetics*
D001786:Blood Glucose; C094335:H19 long non-coding RNA; D007328:Insulin; D062085:RNA, Long Noncoding; D022661:RNA, Untranslated; D007335:Insulin-Like Growth Factor II