Publication Date:
2000-07-06
Description:
Most developing thymocytes undergo apoptosis because they cannot interact productively with molecules encoded by the major histocompatibility complex. Here, we show that mice lacking the orphan nuclear hormone receptor RORgamma lose thymic expression of the anti-apoptotic factor Bcl-xL. RORgamma thus regulates the survival of CD4+8+ thymocytes and may control the temporal window during which thymocytes can undergo positive selection. RORgamma was also required for development of lymph nodes and Peyer's patches, but not splenic follicles. In its absence, there was loss of a population of CD3-CD4+CD45+ cells that normally express RORgamma and that are likely early progenitors of lymphoid organs. Hence, RORgamma has critical functions in T cell repertoire selection and lymphoid organogenesis.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Sun, Z -- Unutmaz, D -- Zou, Y R -- Sunshine, M J -- Pierani, A -- Brenner-Morton, S -- Mebius, R E -- Littman, D R -- New York, N.Y. -- Science. 2000 Jun 30;288(5475):2369-73.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Molecular Pathogenesis Program, Skirball Institute of Biomolecular Medicine and Howard Hughes Medical Institute, New York University School of Medicine, New York, NY 10016, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/10875923" target="_blank"〉PubMed〈/a〉
Keywords:
Animals
;
Apoptosis
;
*CDC2-CDC28 Kinases
;
Cell Count
;
Cell Cycle
;
Cell Survival
;
Crosses, Genetic
;
Cyclin-Dependent Kinase 2
;
Cyclin-Dependent Kinases/metabolism
;
DNA-Binding Proteins/genetics/metabolism
;
Female
;
Gene Targeting
;
Inhibitor of Differentiation Protein 2
;
Lymphoid Tissue/cytology/embryology/*growth & development
;
Male
;
Mice
;
Mice, Inbred C57BL
;
Nuclear Receptor Subfamily 1, Group F, Member 3
;
Protein-Serine-Threonine Kinases/metabolism
;
Proto-Oncogene Proteins c-bcl-2/genetics/metabolism
;
Receptors, Cytoplasmic and Nuclear/genetics/*physiology
;
*Receptors, Retinoic Acid
;
*Receptors, Thyroid Hormone
;
*Repressor Proteins
;
T-Lymphocyte Subsets/*cytology
;
Thymus Gland/*cytology
;
*Transcription Factors
;
bcl-X Protein
Print ISSN:
0036-8075
Electronic ISSN:
1095-9203
Topics:
Biology
,
Chemistry and Pharmacology
,
Computer Science
,
Medicine
,
Natural Sciences in General
,
Physics
