Sox1 directly regulates the gamma-crystallin genes and is essential for lens development in mice.

gamma-Crystallins are major structural components of the lens fiber cells in amphibians and mammals. Many dominant inherited cataracts in humans and mice have been shown to map within the gamma-crystallin gene cluster. Several transcription factors, including PAX6 and SOX proteins, have been suggested as candidates for crystallin gene regulation. Here we show that the targeted deletion of Sox1 in mice causes microphthalmia and cataract. Mutant lens fiber cells fail to elongate, probably as a result of an almost complete absence of gamma-crystallins. It appears that the direct interaction of the SOX1 protein with a promoter element conserved in all gamma-crystallin genes is responsible for their expression.

[1]  J. Mcavoy.  Cell division, cell elongation and the co-ordination of crystallin gene expression during lens morphogenesis in the rat. , 1978, Journal of embryology and experimental morphology.

[2]  J. Horwitz.  Alpha-crystallin can function as a molecular chaperone. , 1992, Proceedings of the National Academy of Sciences of the United States of America.

[3]  P. Gruss,et al.  Current views on eye development , 1997, Trends in Neurosciences.

[4]  E. Cartwright,et al.  Embryonic expression of the chicken Sox2, Sox3 and Sox11 genes suggests an interactive role in neuronal development , 1995, Mechanisms of Development.

[5]  L. Strong,et al.  Positional cloning and characterization of a paired box- and homeobox-containing gene from the aniridia region , 1991, Cell.

[6]  M. Lyon,et al.  Mapping of six dominant cataract genes in the mouse. , 1994, Genomics.

[7]  P. Goodfellow,et al.  A comparison of the properties of Sox-3 with Sry and two related genes, Sox-1 and Sox-2. , 1996, Development.

[8]  L. Tsui,et al.  Temporal regulation of six crystallin transcripts during mouse lens development. , 1992, Experimental eye research.

[9]  R. Lovell-Badge,et al.  Sox genes find their feet. , 1997, Current opinion in genetics & development.

[10]  J. Piatigorsky,et al.  Lens crystallins: the evolution and expression of proteins for a highly specialized tissue. , 1988, Annual review of biochemistry.

[11]  L. Tsui,et al.  Multiple regulatory elements of the murine γ2-crystallin promoter , 1989 .

[12]  A. Cumano,et al.  Defects in cardiac outflow tract formation and pro-B-lymphocyte expansion in mice lacking Sox-4 , 1996, Nature.

[13]  T. Hohman,et al.  Hypertonic stress induces αB-crystallin expression , 1992 .

[14]  Collignon Jv.  Study of a new family of genes relating to the mammalian testis determining gene. , 1992 .

[15]  Peter Goodfellow,et al.  A gene mapping to the sex-determining region of the mouse Y chromosome is a member of a novel family of embryonically expressed genes , 1990, Nature.

[16]  E. Wawrousek,et al.  Targeted disruption of the mouse alpha A-crystallin gene induces cataract and cytoplasmic inclusion bodies containing the small heat shock protein alpha B-crystallin. , 1997, Proceedings of the National Academy of Sciences of the United States of America.

[17]  L. Tsui,et al.  A frameshift mutation in the γE–crystallin gene of the Elo mouse , 1992 .

[18]  R. Lovell-Badge,et al.  Involvement of SOX proteins in lens‐specific activation of crystallin genes. , 1995, The EMBO journal.

[19]  Sahar Mansour,et al.  Campomelic dysplasia and autosomal sex reversal caused by mutations in an SRY-related gene , 1994, Nature.

[20]  L. Tsui,et al.  A locus for a human hereditary cataract is closely linked to the gamma-crystallin gene family. , 1987, Proceedings of the National Academy of Sciences of the United States of America.

[21]  G. Saunders,et al.  Mouse Small eye results from mutations in a paired-like homeobox-containing gene , 1991, Nature.

[22]  J. Piatigorsky,et al.  Enzyme/crystallins: Gene sharing as an evolutionary strategy , 1989, Cell.

[23]  D. Beebe,et al.  Decreased membrane permeability to potassium is responsible for the cell volume increase that drives lens fiber cell elongation , 1988, Journal of cellular physiology.

[24]  Richard L. Maas,et al.  PAX6 gene dosage effect in a family with congenital cataracts, aniridia, anophthalmia and central nervous system defects , 1994, Nature Genetics.

[25]  A. Cvekl,et al.  Lens development and crystallin gene expression: many roles for Pax‐6 , 1996, BioEssays : news and reviews in molecular, cellular and developmental biology.

[26]  R. Lovell-Badge,et al.  Preventing the loss of competence for neural induction: HGF/SF, L5 and Sox-2. , 1997, Development.

[27]  P. Callaerts,et al.  Induction of ectopic eyes by targeted expression of the eyeless gene in Drosophila. , 1995, Science.