UCL logo

UCL Discovery

UCL home » Library Services » Electronic resources » UCL Discovery

Analysis of mouse models carrying the I26T and R160C substitutions in the transcriptional repressor HESX1 as models for septo-optic dysplasia and hypopituitarism

Sajedi, E; Gaston-Massuet, C; Signore, M; Andoniadou, CL; Kelberman, D; Castro, S; Etchevers, HC; ... Martinez-Barbera, JP; + view all (2008) Analysis of mouse models carrying the I26T and R160C substitutions in the transcriptional repressor HESX1 as models for septo-optic dysplasia and hypopituitarism. Disease Models and Mechanisms , 1 (4-5) 241 - 254. 10.1242/dmm.00071. Gold open access

Abstract

A homozygous substitution of the highly conserved isoleucine at position 26 by threonine (I26T) in the transcriptional repressor HESX1 has been associated with anterior pituitary hypoplasia in a human patient, with no forebrain or eye defects. Two individuals carrying a homozygous substitution of the conserved arginine at position 160 by cysteine (R160C) manifest septo-optic dysplasia (SOD), a condition characterised by pituitary abnormalities associated with midline telencephalic structure defects and optic nerve hypoplasia. We have generated two knock-in mouse models containing either the I26T or R160C substitution in the genomic locus. Hesx1I26T/I26Tembryos show pituitary defects comparable with Hesx1–/–mouse mutants, with frequent occurrence of ocular abnormalities, although the telencephalon develops normally. Hesx1R160C/R160Cmutants display forebrain and pituitary defects that are identical to those observed in Hesx1–/–null mice. We also show that the expression pattern of HESX1during early human development is very similar to that described in the mouse, suggesting that the function of HESX1 is conserved between the two species. Together, these results suggest that the I26T mutation yields a hypomorphic allele, whereas R160C produces a null allele and, consequently, a more severe phenotype in both mice and humans.

Type: Article
Title: Analysis of mouse models carrying the I26T and R160C substitutions in the transcriptional repressor HESX1 as models for septo-optic dysplasia and hypopituitarism
Open access status: An open access publication
DOI: 10.1242/dmm.00071
Publisher version: http://dx.doi.org/10.1242/dmm.00071
Language: English
Additional information: Supplementary material for this article is available at http:/​/​dmm.biologists.org/​content/​1/​4–5/​241/​suppl/​DC1
UCL classification: UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Pop Health Sciences > UCL GOS Institute of Child Health
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Pop Health Sciences > UCL GOS Institute of Child Health > ICH Development Bio and Cancer Prog
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Pop Health Sciences > UCL GOS Institute of Child Health > ICH Developmental Neurosciences Prog
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Pop Health Sciences > UCL GOS Institute of Child Health > ICH Genetics and Genomic Medicine Prog
UCL > Provost and Vice Provost Offices > VP Health
UCL > Provost and Vice Provost Offices > VP Health > Translational Research Office
URI: http://discovery.ucl.ac.uk/id/eprint/99378
Downloads since deposit
0Downloads
Download activity - last month
Download activity - last 12 months
Downloads by country - last 12 months

Archive Staff Only

View Item View Item