title: The Samd9L gene: transcriptional regulation and tissue-specific expression in mouse development.
abstract: Normophosphatemic familial tumoral calcinosis (NFTC) is caused by mutations in the SAMD9 gene. This gene is absent in mouse, while there is a murine paralog, Samd9-like (Samd9L). To clarify the relationships between SAMD9 and SAMD9L, we investigated the transcriptional regulation and expression pattern of mouse Samd9L. An ∼1.5-kb mouse Samd9L promoter fragment was cloned, and a series of 5' deletion constructs were linked to a luciferase reporter gene. All constructs showed significant activity in transfected epithelial cells and mouse fibroblasts, and the presence of regulatory cis-elements as close as 87 bp upstream of the transcription start site was identified. Ras-responsive element binding protein 1 (Rreb-1) was identified in this region by protein-DNA binding array. The expression of Samd9L was upregulated by calcitonin, and this was preceded by a significant increase in the expression of Rreb-1 mRNA. Quantitative real-time PCR analysis of Samd9L revealed near-ubiquitous expression, with the highest level in the kidney. Tissue-specific expression was also confirmed both by in situ β-gal staining and quantitative enzymatic activity assay in a transgenic Samd9L(+/-) mouse in which the LacZ gene replaced exon 2 in the Samd9L gene. These findings assist in understanding the regulation of Samd9L in the context of its paralogous gene, SAMD9, which harbors mutations in NFTC.
authors.affiliation: Department of Dermatology and Cutaneous Biology, Jefferson Medical College, Philadelphia, Pennsylvania, USA.
authors.forename: Qiujie
authors.initials: Q
authors.lastname: Jiang
authors.forename: Benjamin
authors.initials: B
authors.lastname: Quaynor
authors.forename: Alex
authors.initials: A
authors.lastname: Sun
authors.forename: Qiaoli
authors.initials: Q
authors.lastname: Li
authors.forename: Hirotaka
authors.initials: H
authors.lastname: Matsui
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Honda
authors.forename: Toshiya
authors.initials: T
authors.lastname: Inaba
authors.forename: Eli
authors.initials: E
authors.lastname: Sprecher
authors.forename: Jouni
authors.initials: J
authors.lastname: Uitto
mesh_terms: D000818:Animals; D002114:Calcinosis / Q000235:genetics; D002116:Calcitonin / Q000502:physiology; D002478:Cells, Cultured; D004268:DNA-Binding Proteins / Q000502:physiology; D047108:Embryonic Development / Q000502:physiology; D005786:Gene Expression Regulation; D006801:Humans; D007668:Kidney / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D009369:Neoplasms / Q000209:etiology; D009928:Organ Specificity; D011401:Promoter Regions, Genetic; D014157:Transcription Factors / Q000502:physiology; D014158:Transcription, Genetic; D025521:Tumor Suppressor Proteins / Q000172:deficiency / Q000235:genetics* / Q000378:metabolism
chemical_list: D004268:DNA-Binding Proteins; C101743:RREB1 protein, human; C560581:Samd9L protein, mouse; D014157:Transcription Factors; D025521:Tumor Suppressor Proteins; D002116:Calcitonin