Details

Autor(en) / Beteiligte

• Aydin, Ebru
• Kloos, Dick-Paul
• Gay, Emmanuel
• Jonker, Willem
• Hu, Lijuan
• Bullwinkel, Jörn
• Brown, Jeremy P
• Manukyan, Maria
• Giera, Martin
• Singh, Prim B
• Fundele, Reinald

Titel

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.