A Double-Deletion Mutation in the Pitx3 Gene Causes Arrested Lens Development in Aphakia Mice

A Double-Deletion Mutation in the Pitx3 Gene Causes Arrested Lens Development in Aphakia Mice The recessive aphakia ( ak ) mouse mutant is characterized by bilateral microphthalmia due to a failure of lens morphogenesis. We fine-mapped the ak locus to the interval between D19Umi1 and D19Mit9, developed new polymorphic markers, and mapped candidate genes by construction of a BAC contig. The Pitx3 gene, known to be expressed in lens primordia, shows zero recombination with the ak mutation on our intersubspecific intercross panel representing 1170 meioses. A recent report described a deletion in the intergenic region between Gbf1 and Pitx3 as the possible ak mutation. Our results differ in that we find not only the distant intergenic deletion, but also a much larger deletion directly in the Pitx3 gene, eliminating exon 1 and extending into intron 1 and the promoter region. Pitx3 transcript levels are severely reduced in ak/ak mice from E11.5 to newborn (5 ± 1% of the wildtype levels at E13.5), while an involvement of the flanking Gbf1 and Cig30 genes in the aberrant lens development is highly unlikely based on expression analysis. We conclude that the ak mutation consists of two deletions, the larger of which removes part of Pitx3, indicating a crucial role of this gene in early lens development. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Genomics Elsevier

A Double-Deletion Mutation in the Pitx3 Gene Causes Arrested Lens Development in Aphakia Mice

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Publisher
Elsevier
Copyright
Copyright © 2001 Academic Press
ISSN
0888-7543
eISSN
1089-8646
DOI
10.1006/geno.2000.6464
Publisher site
See Article on Publisher Site

Abstract

The recessive aphakia ( ak ) mouse mutant is characterized by bilateral microphthalmia due to a failure of lens morphogenesis. We fine-mapped the ak locus to the interval between D19Umi1 and D19Mit9, developed new polymorphic markers, and mapped candidate genes by construction of a BAC contig. The Pitx3 gene, known to be expressed in lens primordia, shows zero recombination with the ak mutation on our intersubspecific intercross panel representing 1170 meioses. A recent report described a deletion in the intergenic region between Gbf1 and Pitx3 as the possible ak mutation. Our results differ in that we find not only the distant intergenic deletion, but also a much larger deletion directly in the Pitx3 gene, eliminating exon 1 and extending into intron 1 and the promoter region. Pitx3 transcript levels are severely reduced in ak/ak mice from E11.5 to newborn (5 ± 1% of the wildtype levels at E13.5), while an involvement of the flanking Gbf1 and Cig30 genes in the aberrant lens development is highly unlikely based on expression analysis. We conclude that the ak mutation consists of two deletions, the larger of which removes part of Pitx3, indicating a crucial role of this gene in early lens development.

Journal

GenomicsElsevier

Published: Feb 15, 2001

References

  • Aphakia (ak), a mouse mutation affecting early eye development: Fine mapping, consideration of candidate genes and altered Pax6 and Six3 gene expression pattern
    Grimm, C.; Chatterjee, B.; Favor, J.; Immervoll, T.; Loster, J.; Klopp, N.; Sandulache, R.; Graw, J.
  • Restoration of half the normal dystrophin sequence in a double-deletion Duchenne muscular dystrophy family
    Hoop, R.C.; Russo, L.S.; Riconda, D.L.; Schwartz, L.S.; Hoffman, E.P.
  • Mucopolysaccharidosis type IVA: Common double deletion in the N -acetylgalactosamine-6-sulfatase gene (GALNS)
    Hori, T.; Tomatsu, S.; Nakashima, Y.; Uchiyama, A.; Fukuda, S.; Sukegawa, K.; Shimozawa, N.; Suzuki, Y.; Kondo, N.; Horiuchi, T.
  • Variation in residual PITX2 activity underlies the phenotypic spectrum of anterior segment developmental disorders
    Kozlowski, K.; Walter, M.A.
  • Human GBF1 is a ubiquitously expressed gene of the sec7 domain family mapping to 10q24
    Mansour, S.J.; Herbrick, J.A.; Scherer, S.W.; Melancon, P.
  • Deletion in the promoter region and altered expression of pitx3 homeobox gene in aphakia mice
    Semina, E.V.; Murray, J.C.; Reiter, R.; Hrstka, R.F.; Graw, J.
  • 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
    Semina, E.V.; Reiter, R.S.; Murray, J.C.
  • Role of a new mammalian gene family in the biosynthesis of very long chain fatty acids and sphingolipids
    Tvrdik, P.; Westerberg, R.; Silve, S.; Asadi, A.; Jakobsson, A.; Cannon, B.; Loison, G.; Jacobsson, A.

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