Congenital hereditary cataracts

Graw, Jochen

doi:10.1387/ijdb.041854jg

Cited by 126 publications

(86 citation statements)

References 160 publications

(107 reference statements)

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“…Sox1 null lenses lose expression of γ-crystallin at E12.5 coincident with the downregulation of the related gene, Sox2 (Nishiguchi et al, 1998). Although loss of γ-crystallin has been linked to cataract formation (reviewed in Graw, 2004), it is reasonable to hypothesize that other genes downstream of Sox1 also contribute to the fiber cell differentiation defect.…”

Section: Resultsmentioning

confidence: 99%

Pax6 is misexpressed in Sox1 null lens fiber cells

Donner

Episkopou

et al. 2007

Gene Expression Patterns

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Sox1 null lens fiber cells fail to elongate and have disrupted expression of gamma crystallin. We have evaluated the expression of Sox1 and Pax6 proteins during critical stages of lens morphogenesis, with particular focus on fiber cell differentiation. While Pax6 and Sox1 are co-expressed during early stages of fiber cell differentiation, Sox1 up-regulation coincides temporally with the down-regulation of Pax6, and these proteins therefore display a striking inverse expression pattern in the lens fiber cell compartment. Furthermore, Pax6 is inappropriately expressed in the fiber cells of Sox1 null mice and the Pax6 target, α5 integrin, is simultaneously misexpressed. Finally, we demonstrate a genetic interaction between Sox1 and Pax6, as Sox1 heterozygosity partially rescues the diameter of Pax6 Sey lenses by increasing the number of cells in the fiber cell compartment.

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Section: Resultsmentioning

confidence: 99%

Pax6 is misexpressed in Sox1 null lens fiber cells

Donner

Episkopou

et al. 2007

Gene Expression Patterns

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“…GPR161 is then an appropriate candidate for future mutational analysis for these disorders and human embryonic hydromyelia and congenital cataracts. This approach has been successful for congenital cataracts, where several genes that are mutated in the mouse are also affected in humans with the disease (PAX6, PITX3, FOXE3) (36). Given the modifiability of the mutant phenotypes, vl is also a useful mouse model for studying the more common forms of these diseases like lumbar-sacral spina bifida and age-related cataracts.…”

Section: Discussionmentioning

confidence: 99%

The orphan G protein-coupled receptor, Gpr161 , encodes the vacuolated lens locus and controls neurulation and lens development

Matteson

Desai

Korstanje

et al. 2008

Proc. Natl. Acad. Sci. U.S.A.

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The vacuolated lens (vl) mouse mutant causes congenital cataracts and neural tube defects (NTDs), with the NTDs being caused by abnormal neural fold apposition and fusion. Our positional cloning of vl indicates these phenotypes result from a deletion mutation in an uncharacterized orphan G protein-coupled receptor (GPCR), Gpr161. Gpr161 displays restricted expression to the lateral neural folds, developing lens, retina, limb, and CNS. Characterization of the vl mutation indicates that C-terminal tail of Gpr161 is truncated, leading to multiple effects on the protein, including reduced receptor-mediated endocytosis. We have also mapped three modifier quantitative trait loci (QTL) that affect the incidence of either the vl cataract or NTD phenotypes. Bioinformatic, sequence, genetic, and functional data have determined that Foxe3, a key regulator of lens development, is a gene responsible for the vl cataract-modifying phenotype. These studies have extended our understanding of the vl locus in three significant ways. One, the cloning of the vl locus has identified a previously uncharacterized GPCR-ligand pathway necessary for neural fold fusion and lens development, providing insight into the molecular regulation of these developmental processes. Two, our QTL analysis has established vl as a mouse model for studying the multigenic basis of NTDs and cataracts. Three, we have identified Foxe3 as a genetic modifier that interacts with Gpr161 to regulate lens development.cataracts ͉ Foxe3 ͉ spina bifida

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“…The lens is composed of fiber cells which differentiate from lens epithelial cells through a complex program of structural and genetic changes that continues throughout the lifespan of the organism (Al-Ghoul et al, 2003;Graw, 2004). In contrast to other tissues, the lens has no blood supply, thus the fiber cells at the center of the lens are dependent on a gap junction network that facilitates the exchange of electrolytes and metabolites (Al-Ghoul et al, 2003).…”

Section: Functional Relationships Between Connexins and Aquaporins Amentioning

confidence: 99%

Interactions of connexins with other membrane channels and transporters

Chanson

Kotsias

Peracchia

et al. 2007

Progress in Biophysics and Molecular Biology

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Cell-to-cell communication through gap junctions exists in most animal cells and is essential for many important biological processes including rapid transmission of electric signals to coordinate contraction of cardiac and smooth muscle, the intercellular propagation of Ca 2+ waves and synchronization of physiological processes between adjacent cells within a tissue. Recent studies have shown that connexins can have either direct or indirect interactions with other plasma membrane ion channels or membrane transport proteins with important functional consequences. For example, in tissues most severely affected by cystic fibrosis, activation of the Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) has been shown to influence connexin function. Moreover, a direct interaction between Cx45.6 and the Major Intrinsic Protein/AQP0 in lens appears to influence the process of cell differentiation whereas interactions between aquaporin 4 (AQP4) and Cx43 in mouse astrocytes may coordinate the intercellular movement of ions and water between astrocytes. In this review, we discuss evidence supporting interactions between connexins and membrane channels/ transporters including CFTR, aquaporins, ionotropic glutamate receptors, and between pannexin1, another class of putative gap-junction-forming proteins, and Kvβ3, a regulatory β-subunit of voltage gated potassium channels. Although the precise molecular nature of these interactions has yet to be defined, their consequences may be critical for normal tissue homeostasis.

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Congenital hereditary cataracts

Cited by 126 publications

References 160 publications

Pax6 is misexpressed in Sox1 null lens fiber cells

Pax6 is misexpressed in Sox1 null lens fiber cells

The orphan G protein-coupled receptor, Gpr161 , encodes the vacuolated lens locus and controls neurulation and lens development

Interactions of connexins with other membrane channels and transporters

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