Samd4-flox Mouse

Samd4, part of the SAMD4 protein family, is a novel RNA-binding protein. It can mediate post-transcriptional regulation and translation repression in eukaryotes [2]. The SAMD4 protein family in mammalian cells consists of SAMD4A/Smaug1 and SAMD4B/Smaug2, both containing a common SAM domain to bind to target mRNAs and regulate their stability, degradation, and translation [2]. Samd4 is involved in multiple biological pathways, such as the mTOR/OXPHOS axis [3], and is of great biological importance in processes like cardiac regeneration, skeleton development, and in pathological conditions including cancer, myopathy, and neurodegenerative diseases [1,2,4,5]. Genetic models, especially KO/CKO mouse models, are valuable for studying its functions.

In KO mouse models, Samd4 deficiency led to multiple developmental defects. Mice lacking Samd4 had delayed bone development, decreased osteogenesis, and chondrocyte defects due to increased MIG6 protein synthesis as SAMD4 usually binds Mig6 mRNA to inhibit its translation [4]. A Samd4 missense mutation in mice caused leanness, myopathy, uncoupled mitochondrial respiration, and dysregulated mTORC1 signaling, likely due to hypophosphorylation of 4E-BP1 and S6 in muscle and adipose tissues [6]. VSMC-specific knockout of SAMD4A exacerbated pancreatic elastase-induced abdominal aortic aneurysm formation, while VSMC knock-in attenuated it, with SAMD4A regulating VSMC contraction by binding to KDM2B [7].

In conclusion, Samd4 plays essential roles in regulating protein translation, which is crucial for processes like bone development and mitochondrial function. KO/CKO mouse models have revealed its significance in diseases such as skeletal disorders, myopathy, and abdominal aortic aneurysm. Understanding Samd4's functions can potentially provide new therapeutic strategies for these associated diseases.