Deficiency of SHP-1 protein-tyrosine phosphatase in "viable motheaten" mice results in retinal degeneration.
Invest Ophthalmol Vis Sci
; 47(3): 1201-9, 2006 Mar.
Article
em En
| MEDLINE
| ID: mdl-16505059
ABSTRACT
PURPOSE:
Viable motheaten mutant mice (abbreviated allele symbol me(v)) are deficient in Src-homology 2-domain phosphatase (SHP)-1, a critical negative regulator of signal transduction in hematopoietic cells. These mice exhibit immune dysfunction, hyperproliferation of myeloid cells, and regenerative anemia. This study focused on the role of SHP-1 in retinal homeostasis.METHODS:
Ophthalmoscopy, histology, transmission electron microscopy (TEM), electroretinography (ERG), immunohistochemistry, Western blot, bone marrow transplantation, and genetic crosses were performed for phenotypic characterization and functional studies of retinal degeneration (RD) in me(v)/me(v) mice.RESULTS:
Fundus examinations of me(v)/me(v) mice revealed numerous, small white spots. Histologic examination demonstrated photoreceptor loss beginning at 3 weeks of age, and TEM revealed disorganization and reduction in the number of outer segments, as well as the presence of phagocytic cells in the subretinal space. Rod- and cone-mediated ERGs were abnormal. SHP-1 protein was expressed in mouse and human retinal lysates and was localized to the outer nuclear layer of the retina in me(v)/me(v) and control mice. Autoantibodies are not necessary for RD, as B-cell-deficient me(v)/me(v) Igh-6(tm1Cgn) mice had no attenuation of photoreceptor cell loss compared with age-matched me(v)/me(v) mice. Histologic examination of lungs and retinas from normal recipients of me(v)/me(v) marrow revealed the classic acidophilic macrophage pneumonia of me(v)/me(v) mice, but no retinal degeneration.CONCLUSIONS:
me(v)/me(v) mice exhibit normal retinal development with the onset of RD at 3 weeks of age and a rapidly progressive loss of photoreceptors. These findings support the hypothesis that SHP-1 plays a critical role in retinal homeostasis.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Degeneração Retiniana
/
Proteínas Tirosina Fosfatases
/
Peptídeos e Proteínas de Sinalização Intracelular
Limite:
Animals
Idioma:
En
Revista:
Invest Ophthalmol Vis Sci
Ano de publicação:
2006
Tipo de documento:
Article
País de afiliação:
Estados Unidos