The Samd9L Gene: Transcriptional regulation and tissue-specific expression in mouse development

Qiujie Jiang, Benjamin Quaynor, Alex Sun, Qiaoli Li, Hirotaka Matsui, Hiroaki Honda, Toshiya Inaba, Eli Sprecher, Jouni Uitto

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish
Pages (from-to)1428-1434
Number of pages7
JournalJournal of Investigative Dermatology
Volume131
Issue number7
DOIs
StatePublished - Jul 2011
Externally publishedYes

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