Faculty Collaboration Database

Isolation of a new homeobox gene belonging to the Pitx/Rieg family: expression during lens development and mapping to the aphakia region on mouse chromosome 19. Hum Mol Genet 1997 Nov;6(12):2109-16

Date

11/05/1997

Pubmed ID

9328475

DOI

10.1093/hmg/6.12.2109

Scopus ID

2-s2.0-0030669179 (requires institutional sign-in at Scopus site)   172 Citations

Abstract

We recently reported the positional cloning of a homeobox gene involved in the pathogenesis of Rieger syndrome, RIEG1 , and its mouse homolog, Rieg1 . Rieg1 (also independently described as Pitx2) is highly homologous to the Ptx1/Potx gene product, suggesting that there may be additional members of this novel Pitx family. The Pitx genes play an important role in eye, tooth, pituitary and umbilical region development as evidenced by Rieger syndrome and iris hypoplasia phenotypes, resulting from mutations in the RIEG1 gene and by expression studies. In order to characterize further the Pitx gene family we searched mouse cDNA libraries to identify additional members. A new gene was isolated which encodes a homeoprotein with strong homology to the other Pitx proteins and 97-100% identity in the homeodomain itself, suggesting that this is a third member of the family, Pitx3 . In whole mount in situ hybridization on mouse embryos ranging from 8.5 to 11.5 days post-coitum (d.p.c.), Pitx3 mRNA was seen only in the developing lens starting at day 11. Hybridization on cross-sections revealed strong signals in the lens vesicle in 11 d.p.c. embryos and throughout the lens, particularly in the anterior epithelium and equator region in 15 d.p.c. embryos. Pitx3 was mapped close to aphakia on mouse chromosome 19. The aphakia homozygous mouse is characterized by small eyes lacking a lens, which fail to develop beyond 11 d.p.c. These data make Pitx3 a strong candidate gene for the aphakia phenotype in the mouse and suggest a role for the human homolog in congenital lens malformations.

Author List

Semina EV, Reiter RS, Murray JC

Author

Elena V. Semina PhD Chief, Professor in the Ophthalmology and Visual Sciences department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Amino Acid Sequence
Animals
Aphakia
Base Sequence
Chromosome Mapping
DNA, Complementary
Embryonic and Fetal Development
Exons
Gene Expression Regulation, Developmental
Genes, Homeobox
Homeodomain Proteins
Introns
Lens, Crystalline
Mice
Mice, Inbred C57BL
Molecular Sequence Data
Multigene Family
Mutation
Nuclear Proteins
Paired Box Transcription Factors
Transcription Factors