The Sgp3 locus derived from the 129 strain is responsible for enhanced endogenous retroviral expression in macroH2A1-deficient mice

Autor: Lakshmi Changolkar, John R. Pehrson, Shozo Izui, Lucie Clementine Baudino
Jazyk: angličtina
Rok vydání: 2010
Předmět:
Candidate gene
Mice
129 Strain
Immunology
Congenic
Endogenous retrovirus
Locus (genetics)
Molecular Chaperones/genetics
ddc:616.07
Hepatocytes/*metabolism/pathology
Article
Viral Envelope Proteins/genetics/*metabolism
Histones
03 medical and health sciences
Mice
0302 clinical medicine
Retrovirus
Viral Envelope Proteins
Lupus Erythematosus
Systemic/*genetics/immunology
Immunology and Allergy
Lupus Erythematosus
Systemic
Animals
Humans
Gene
Endogenous Retroviruses/*physiology
Gene knockout
030304 developmental biology
Glycoproteins
Regulation of gene expression
Genetics
0303 health sciences
Histones/genetics
biology
Mice
Inbred NZB
Endogenous Retroviruses
Glycoproteins/genetics
biology.organism_classification
Molecular biology
Lupus Nephritis
Mice
Inbred C57BL
Disease Models
Animal
Gene Expression Regulation
Lupus Nephritis/*genetics/immunology
Hepatocytes
030215 immunology
Molecular Chaperones
Zdroj: Journal of Autoimmunity, Vol. 35, No 4 (2010) pp. 398-403
Journal of autoimmunity
ISSN: 0896-8411
Popis: The endogenous retroviral envelope glycoprotein, gp70, implicated in murine lupus nephritis is secreted by hepatocytes, and its expression is largely regulated by the Sgp3 (serum gp70 production 3) locus derived from lupus-prone mice. Because of the localization of the macroH2A1 gene encoding macroH2A histone variants within the Sgp3 interval and of an up-regulated transcription of endogenous retroviral sequences in macroH2A1-deficient C57BL/6 (B6) mice, we investigated whether macroH2A1 is a candidate gene for Sgp3. macroH2A1-deficient B6 mice carrying the 129-derived Sgp3 locus, which was co-transferred with the 129 macroH2A1 mutant gene, displayed increased levels of serum gp70 and hepatic retroviral gp70 RNAs comparable to those of B6.NZB-Sgp3 congenic mice bearing the Sgp3 locus of lupus-prone NZB mice. In contrast, the abundance of retroviral gp70 RNAs in macroH2A1-deficient 129 mice was not elevated at all as compared with wild-type 129 mice. Furthermore, Sgp3 subcongenic B6 mice devoid of the NZB-derived macroH2A1 gene displayed an Sgp3 phenotype identical to that of B6.NZB-Sgp3 congenic mice carrying the NZB-derived macroH2A1 gene, thus excluding macroH2A1 as a candidate Sgp3 gene. Collectively, our data indicate that enhanced transcription of endogenous retroviral sequences observed in macroH2A1-deficient B6 mice is not a result of the macroH2A1 mutation, but due to the presence of the 129-derived Sgp3 locus. In contrast, the effect of a macroH2A1 knockout mutation on the expression of several non-retroviral cellular genes was very similar on the B6 and 129 backgrounds, indicating that these effects were due to the macroH2A1 knockout.
Databáze: OpenAIRE
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