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A hypomorphic Cbx3 allele causes prenatal growth restriction and perinatal energy homeostasis defects
Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Organismal Biology, Evolution and Developmental Biology.
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2015 (English)In: Journal of Biosciences, ISSN 0250-5991, E-ISSN 0973-7138, Vol. 40, no 2, 325-338 p.Article in journal (Refereed) Published
Abstract [en]

Mammals have three HP1 protein isotypes HP1 beta (CBX1), HPl gamma (CBX3) and HP1 alpha (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 ChX3(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.

Place, publisher, year, edition, pages
2015. Vol. 40, no 2, 325-338 p.
Keyword [en]
Brown adipose tissue, HP1, Igf2P0, placental development, Upc1
National Category
Biological Sciences
URN: urn:nbn:se:uu:diva-256821DOI: 10.1007/s12038-015-9520-xISI: 000355068100013PubMedID: 25963260OAI: oai:DiVA.org:uu-256821DiVA: diva2:827335
Available from: 2015-06-26 Created: 2015-06-26 Last updated: 2015-06-26Bibliographically approved

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