title: Evidence that postnatal growth retardation in XO mice is due to haploinsufficiency for a non-PAR X gene.
abstract: XO Turner women, irrespective of the parental source of the X chromosome, are of short stature, and this is now thought to be largely a consequence of haploinsufficiency for the pseudoautosomal region (PAR) gene SHOX. X(p)O mice (with a paternal X) are developmentally retarded in fetal life, are underweight at birth, and show reduced weight gain in the first few weeks after birth. X(m)O mice, on the other hand, are more developmentally advanced than their XX siblings in fetal life; their postnatal growth has not hitherto been assessed. Here we show that X(m)O mice are not underweight at birth, but they nevertheless show reduced weight gain postnatally. The fact that postnatal growth is affected in X(p)O and X(m)O mice, means that this must be due to X dosage deficiency. In order to see if haploinsufficiency for a PAR gene was responsible for this growth deficit (cf SHOX deficiency in Turner women), X(m)Y*(X) females, in which the Y*(X) chromosome provides a second copy of the PAR, were compared with XX females. These X(m)Y*(X) females were also growth-retarded relative to their XX sibs, suggesting that it may be haploinsufficiency for a non-dosage-compensated X gene or genes outside the PAR that is responsible for the postnatal growth deficit in XO mice. The X genes known to escape X inactivation in the mouse have closely similar Y homologues. X(m)YSRY-negative females were therefore compared with XX females to see if the presence of the SRY-negative Y chromosome corrected the growth deficit; this proved to be the case. The postnatal growth deficit of XO mice is therefore probably due to haploinsufficiency for a non-dosage-compensated X gene that has a Y homologue that provides an equivalent function in the somatic tissues of males.
authors.affiliation: Division of Developmental Genetics, MRC National Institute for Medical Research, London, UK. pburgoy@nimr.mrc.ac.uk
authors.forename: P S
authors.initials: PS
authors.lastname: Burgoyne
authors.forename: O A
authors.initials: OA
authors.lastname: Ojarikre
authors.forename: J M A
authors.initials: JM
authors.lastname: Turner
mesh_terms: D000818:Animals; D001724:Birth Weight; D003433:Crosses, Genetic; D005260:Female; D005838:Genotype; D006130:Growth Disorders / Q000235:genetics* / Q000473:pathology; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D008815:Mice, Inbred Strains; D008817:Mice, Mutant Strains; D012729:Sex Chromosome Aberrations; D013997:Time Factors; D014960:X Chromosome / Q000235:genetics*