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A hypomorphic Cbx3 allele causes prenatal growth restriction and perinatal energy homeostasis defects
Ist Teil von
Journal of biosciences, 2015-06, Vol.40 (2), p.325-338
Ort / Verlag
New Delhi: Springer India
Erscheinungsjahr
2015
Quelle
MEDLINE
Beschreibungen/Notizen
ABSTRACT
Mammals have three HP1 protein isotypes HP1β (CBX1), HP1γ (CBX3) and HP1α (CBX5) that are encoded by the corresponding genes
Cbx1, Cbx3
and
Cbx5
. Recent work has shown that reduction of CBX3 protein in homozygotes for a hypomorphic allele (
Cbx3
hypo
) causes a severe postnatal mortality with around 99% of the homozygotes dying before weaning. It is not known what the causes of the postnatal mortality are. Here we show that
Cbx3
hypo/hypo
conceptuses are significantly reduced in size and the placentas exhibit a haplo-insufficiency. Late gestation
Cbx3
hypo/hypo
placentas have reduced mRNA transcripts for genes involved in growth regulation, amino acid and glucose transport. Blood vessels within the
Cbx3
hypo/hypo
placental labyrinth are narrower than wild-type. Newborn
Cbx3
hypo/hypo
pups are hypoglycemic, the livers are depleted of glycogen reserves and there is almost complete loss of stored lipid in brown adipose tissue (BAT). There is a 10-fold reduction in expression of the BAT-specific
Ucp1
gene, whose product is responsible for non-shivering themogenesis. We suggest that it is the small size of the
Cbx3
hypo/hypo
neonates, a likely consequence of placental growth and transport defects, combined with a possible inability to thermoregulate that causes the severe postnatal mortality.