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  Mutations at the mouse ichthyosis locus are within the lamin B receptor gene: a single gene model for human Pelger-Huet anomaly

Shultz, L. D., Lyons, B. L., Burzenski, L. M., Gott, B., Samuels, R., Schweitzer, P. A., et al. (2003). Mutations at the mouse ichthyosis locus are within the lamin B receptor gene: a single gene model for human Pelger-Huet anomaly. Human Molecular Genetics, 12(1), 61-69.

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Item Permalink: http://hdl.handle.net/11858/00-001M-0000-0010-8AF7-6 Version Permalink: http://hdl.handle.net/11858/00-001M-0000-0010-8AF8-4
Genre: Journal Article
Alternative Title : Hum. Mol. Genet.

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 Creators:
Shultz, Leonhard D., Author
Lyons, Bonnie L., Author
Burzenski, Lisa M., Author
Gott, Bruce, Author
Samuels, Rebecca, Author
Schweitzer, Peter A., Author
Dreger, Christine, Author
Herrmann, Harald, Author
Kalscheuer, Vera1, Author              
Olins, Ada L., Author
Olins, Donald E., Author
Sperling, Karl, Author
Hoffmann, Katrin2, Author              
Affiliations:
1Chromosome Rearrangements and Disease (Vera Kalscheuer), Dept. of Human Molecular Genetics (Head: Hans-Hilger Ropers), Max Planck Institute for Molecular Genetics, Max Planck Society, ou_1479642              
2Research Group Development & Disease (Head: Stefan Mundlos), Max Planck Institute for Molecular Genetics, Max Planck Society, ou_1433557              

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 Abstract: The nature of the wild-type gene product at the mouse ichthyosis (ic) locus has been of great interest because mutations at this locus cause marked abnormalities in nuclear heterochromatin, similar to those observed in Pelger–Huët anomaly (PHA). We recently found that human PHA is caused by mutations in the gene (LBR) encoding lamin B receptor, an evolutionarily conserved inner nuclear membrane protein involved in nuclear assembly and chromatin binding. Mice homozygous for deleterious alleles at the ichthyosis (ic) locus present with a blood phenotype similar to PHA, and develop other phenotypic abnormalities, including alopecia, variable expression of syndactyly and hydrocephalus. The ic locus on mouse chromosome 1 shares conserved synteny with the chromosomal location of the human LBR locus on human chromosome 1. In this study, we identified one nonsense (815ins) and two frameshift mutations (1088insCC and 1884insGGAA) within the Lbr gene of mice homozygous for either of three independent mutations (ic, icJ and ic4J, respectively) at the ichthyosis locus. These allelic mutations are predicted to result in truncated or severely impaired LBR protein. Our studies of mice homozygous for the icJ mutation revealed a complete loss of LBR protein as shown by immunofluorescence microscopy and immunoblotting. The findings provide the molecular basis for the heterochromatin clumping and other distinct phenotypes caused by ic mutations. These spontaneous Lbr mutations confirm the molecular basis of human PHA and provide a small animal model for determination of the precise function of LBR in normal and pathological states.

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Language(s): eng - English
 Dates: 2003-01
 Publication Status: Published in print
 Pages: -
 Publishing info: -
 Table of Contents: -
 Rev. Type: -
 Identifiers: eDoc: 173613
ISI: 000180161000007
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Title: Human Molecular Genetics
  Alternative Title : Hum. Mol. Genet.
Source Genre: Journal
 Creator(s):
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Publ. Info: -
Pages: - Volume / Issue: 12 (1) Sequence Number: - Start / End Page: 61 - 69 Identifier: ISSN: 0964-6906