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Publication : 1 kb of 5' flanking sequence from mouse MC4R gene is sufficient for tissue specific expression in a transgenic mouse.

First Author  Daniel PB Year  2005
Journal  Mol Cell Endocrinol Volume  239
Issue  1-2 Pages  63-71
PubMed ID  15950372 Mgi Jnum  J:99300
Mgi Id  MGI:3581947 Doi  10.1016/j.mce.2005.03.013
Citation  Daniel PB, et al. (2005) 1kb of 5' flanking sequence from mouse MC4R gene is sufficient for tissue specific expression in a transgenic mouse. Mol Cell Endocrinol 239(1-2):63-71
abstractText  The melanocortin 4 receptor (MC4R) plays a critical role in the regulation of energy homeostasis, and the MC4R knockout mouse and humans with MC4R defective mutations in only one allele indicate that there is a gene dosage effect. Alterations in gene expression levels for MC4R could, therefore, have significant effects on energy homeostasis. To begin to develop a mouse model for studies on MC4R promoter in situ we used approximately 1kb mouse MC4R promoter together with 426bp MC4R 5' UTR, previously shown to support basal expression of reporter gene transcription in cell lines with endogenous MC4R mRNA, and fused this DNA to a nuclear localized LacZ reporter gene. The construct was injected into pronuclei from FVB mice. Five transgenic lines were identified as carrying autosomal transgene insertions; three of these had significant beta-galactosidase staining in brain and in a few cells in the heart but not in kidney, liver, lung, gonadal fat or testis. The pattern of transgene expression in the brain differed markedly for the three lines, and in one of these lines was remarkably similar to endogenous MC4R mRNA expression observed using in situ hybridisation. In conclusion, approximately 1kb mouse MC4R promoter is sufficient to direct gene expression to the brain including regions that express endogenous MC4R mRNA.
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