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A Novel Role for the Ostm1 Osteopetr...

Griffiths, Adam.

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A Novel Role for the Ostm1 Osteopetrotic Gene in Neuronal Homeostasis.

Record Type:	Language materials, printed : Monograph/item
Title/Author:	A Novel Role for the Ostm1 Osteopetrotic Gene in Neuronal Homeostasis./
Author:	Griffiths, Adam.
Description:	117 p.
Notes:	Source: Masters Abstracts International, Volume: 49-02, page: .
Contained By:	Masters Abstracts International49-02.
Subject:	Biology, Neuroscience. -
Online resource:	http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=MR66121
ISBN:	9780494661215

A Novel Role for the Ostm1 Osteopetrotic Gene in Neuronal Homeostasis.
Griffiths, Adam.

A Novel Role for the Ostm1 Osteopetrotic Gene in Neuronal Homeostasis. - 117 p.

Source: Masters Abstracts International, Volume: 49-02, page: .

Thesis (M.Sc.)--McGill University (Canada), 2010.

Osteopetrosis is a genetic disease characterized by an excess of bone resulting from a defect in the bone resorbing osteoclasts. The discovery by our lab of the Osteopetrosis associated transmembrane protein 1 ( Ostm1) gene responsible for the most severe recessive osteopetrosis in both grey-lethal (gl/gl) mice and humans provides us with the unique opportunity to decipher the role of this novel protein in a normal and pathological context. Functional rescue was undertaken by directing Ostm1 expression in multiple hematopoietic lineages including osteoclasts with a PU1-Ostm1-BAC transgene. These mice show complete rescue of the standard bone and hematopoietic osteopetrotic phenotypes however they still die prematurely. Knowing Ostm1 is highly expressed in brain tissue, we hypothesized that death was associated with CNS defects. These mice consistently display a severe neurodegenerative phenotype with stimulation of autophagy. To demonstrate the functional link of Ostm1 with the CNS we developed mouse models targeting Ostm1 to neuronal cells and astrocytes by using the specific Synapsin and GFAP promoters respectively. By rescue of neurodegeneration in these gl/gl transgenic mice using the Synapsin promoter, we established a major role for Ostm1 in neuronal cells independent of the hematopoietic and osteoclast defects.

ISBN: 9780494661215Subjects--Topical Terms:

1017680
Biology, Neuroscience.

A Novel Role for the Ostm1 Osteopetrotic Gene in Neuronal Homeostasis.
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100 1 $a Griffiths, Adam. $3 1673334
245 1 2 $a A Novel Role for the Ostm1 Osteopetrotic Gene in Neuronal Homeostasis.
300 $a 117 p.
500 $a Source: Masters Abstracts International, Volume: 49-02, page: .
502 $a Thesis (M.Sc.)--McGill University (Canada), 2010.
520 $a Osteopetrosis is a genetic disease characterized by an excess of bone resulting from a defect in the bone resorbing osteoclasts. The discovery by our lab of the Osteopetrosis associated transmembrane protein 1 ( Ostm1) gene responsible for the most severe recessive osteopetrosis in both grey-lethal (gl/gl) mice and humans provides us with the unique opportunity to decipher the role of this novel protein in a normal and pathological context. Functional rescue was undertaken by directing Ostm1 expression in multiple hematopoietic lineages including osteoclasts with a PU1-Ostm1-BAC transgene. These mice show complete rescue of the standard bone and hematopoietic osteopetrotic phenotypes however they still die prematurely. Knowing Ostm1 is highly expressed in brain tissue, we hypothesized that death was associated with CNS defects. These mice consistently display a severe neurodegenerative phenotype with stimulation of autophagy. To demonstrate the functional link of Ostm1 with the CNS we developed mouse models targeting Ostm1 to neuronal cells and astrocytes by using the specific Synapsin and GFAP promoters respectively. By rescue of neurodegeneration in these gl/gl transgenic mice using the Synapsin promoter, we established a major role for Ostm1 in neuronal cells independent of the hematopoietic and osteoclast defects.
590 $a School code: 0781.
650 4 $a Biology, Neuroscience. $3 1017680
650 4 $a Biology, Genetics. $3 1017730
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710 2 $a McGill University (Canada). $3 1018122
773 0 $t Masters Abstracts International $g 49-02.
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