C57BL/6JCya-Miosem1/Cya
Common Name:
Mios-KO
Product ID:
S-KO-17705
Background:
C57BL/6JCya
Product Type
Age
Genotype
Sex
Quantity
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Basic Information
Strain Name
Mios-KO
Strain ID
KOCMP-252875-Mios-B6J-VB
Gene Name
Product ID
S-KO-17705
Gene Alias
-
Background
C57BL/6JCya
NCBI ID
Modification
Conventional knockout
Chromosome
6
Phenotype
Document
Application
--
Note: When using this mouse strain in a publication, please cite “C57BL/6JCya-Miosem1/Cya mice (Catalog S-KO-17705) were purchased from Cyagen.”
Strain Description
Ensembl Number
ENSMUST00000040017
NCBI RefSeq
NM_145374
Target Region
Exon 3~4
Size of Effective Region
~2.6 kb
Detailed Document
Overview of Gene Research
Mios is a component of the GATOR2 complex, which is essential for amino acids to activate mechanistic target of rapamycin complex 1 (mTORC1) [1,2,3,4,5]. mTORC1 controls growth by regulating anabolic and catabolic processes in response to environmental cues, such as nutrients [1]. The GATOR2-GATOR1 signaling axis is crucial for amino-acid-dependent mTORC1 activation, and Mios, along with other GATOR2 subunits (WDR24, WDR59, SEH1L, and SEC13), is necessary for this activation [1,3,5]. Genetic models, like KO or CKO mouse models, can potentially help in further understanding its role.
Disruption of the Ring domains of Mios, along with those of WDR24 or WDR59, completely blocks amino-acid-mediated mTORC1 activation. Mechanistically, the Ring domain of Mios acts as a hub to maintain GATOR2 integrity, and its disruption leads to self-ubiquitination of WDR24. Physiologically, leucine stimulation dissociates Sestrin2 from the Ring domain of WDR24, contributing to GATOR2-mediated GATOR1 inactivation. WDR24 ablation or Ring deletion in mice prevents mTORC1 activation, resulting in severe growth defects and embryonic lethality at E10.5 [3]. In Dictyostelium discoideum, ablation of MIOS leads to loss of the autophagy-induction and mTORC1-inhibition effects of Tanshinone IIA (T2A), indicating MIOS is involved in T2A-regulated autophagy and mTORC1 inhibition [4].
In conclusion, Mios is essential for the GATOR2-mediated activation of mTORC1 in response to amino acids. The study of Mios through mouse models, such as those with disrupted Ring domains, reveals its significance in embryonic development and nutrient-sensing-related processes. Additionally, its role in the regulation of autophagy and mTORC1 by T2A in Dictyostelium discoideum provides insights into potential therapeutic targets, especially in diseases related to abnormal mTORC1 regulation like glioblastoma [3,4].
References:
1. Valenstein, Max L, Rogala, Kacper B, Lalgudi, Pranav V, Quast, Jan-Philipp, Sabatini, David M. 2022. Structure of the nutrient-sensing hub GATOR2. In Nature, 607, 610-616. doi:10.1038/s41586-022-04939-z. https://pubmed.ncbi.nlm.nih.gov/35831510/
2. Wilson, Miranda L, Romano, Shannon N, Khatri, Nitya, Draper, Bruce W, Marlow, Florence L. 2024. Rbpms2 promotes female fate upstream of the nutrient sensing Gator2 complex component Mios. In Nature communications, 15, 5248. doi:10.1038/s41467-024-49613-2. https://pubmed.ncbi.nlm.nih.gov/38898112/
3. Jiang, Cong, Dai, Xiaoming, He, Shaohui, Xiao, Jianru, Wei, Wenyi. 2022. Ring domains are essential for GATOR2-dependent mTORC1 activation. In Molecular cell, 83, 74-89.e9. doi:10.1016/j.molcel.2022.11.021. https://pubmed.ncbi.nlm.nih.gov/36528027/
4. Shinhmar, Sonia, Schaf, Judith, Lloyd Jones, Katie, Beesley, Philip, Williams, Robin S B. 2024. Developing a Tanshinone IIA Memetic by Targeting MIOS to Regulate mTORC1 and Autophagy in Glioblastoma. In International journal of molecular sciences, 25, . doi:10.3390/ijms25126586. https://pubmed.ncbi.nlm.nih.gov/38928292/
5. Bar-Peled, Liron, Chantranupong, Lynne, Cherniack, Andrew D, Meyerson, Matthew, Sabatini, David M. . A Tumor suppressor complex with GAP activity for the Rag GTPases that signal amino acid sufficiency to mTORC1. In Science (New York, N.Y.), 340, 1100-6. doi:10.1126/science.1232044. https://pubmed.ncbi.nlm.nih.gov/23723238/
Quality Control Standard
Sperm Test
Pre-cryopreservation: Measurement of sperm concentration, determination of sperm viability.
Post-cryopreservation: A vial of cryopreserved sperms is selected for in-vitro fertilization from each batch.
Environmental Standards:SPF
Available Region:Global
Source:Cyagen