C57BL/6JCya-Mcoln1em1/Cya
Common Name:
Mcoln1-KO
Product ID:
S-KO-20346
Background:
C57BL/6JCya
Product Type
Age
Genotype
Sex
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Basic Information
Strain Name
Mcoln1-KO
Strain ID
KOCMP-94178-Mcoln1-B6J-VA
Gene Name
Product ID
S-KO-20346
Gene Alias
2210015I05Rik; TRPML1; mucolipidin
Background
C57BL/6JCya
NCBI ID
Modification
Conventional knockout
Chromosome
8
Phenotype
Document
Application
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Note: When using this mouse strain in a publication, please cite “C57BL/6JCya-Mcoln1em1/Cya mice (Catalog S-KO-20346) were purchased from Cyagen.”
Strain Description
Ensembl Number
ENSMUST00000004683
NCBI RefSeq
NM_053177
Target Region
Exon 2~12
Size of Effective Region
~7.8 kb
Detailed Document
Overview of Gene Research
Mcoln1, also known as TRPML1, is a nonselective cationic channel specifically located in the late endosome and lysosome. It mediates the release of divalent cations like Ca2+, Zn2+ and Fe2+ from the lysosome to the cytosol, playing a crucial role in multiple cellular events such as endocytosis, exocytosis, lysosomal biogenesis, and especially in macroautophagy/autophagy [3].
Activating Mcoln1, either by increasing its expression or using agonists like ML-SA5 or MK6-83, arrests autophagic flux in cancer cells. It does this by perturbing the fusion between autophagosomes and lysosomes through mediating zinc influx. Zinc influx blocks the interaction between STX17 in the autophagosome and VAMP8 in the lysosome, disrupting the fusion process determined by these two SNARE proteins. Agonist-activated Mcoln1 also triggers cancer cell death through autophagic arrest, apoptotic response, and cell cycle arrest, with minimal impact on normal cells [1]. In addition, Mcoln1-mediated autophagy inhibition suppresses cancer metastasis. It leads to damaged mitochondria accumulation and ROS release, which then activates TP53 to modulate the expression of its downstream targets involved in the metastatic cascade [2]. In myocardial ischemia-reperfusion (I/R) injury, Mcoln1 activation secondary to ROS elevation post-I/R blocks autophagic flux in cardiomyocytes by disrupting the fusion between autophagosomes and lysosomes, impairing mitochondrial function and contributing to cardiomyocyte death. Blocking Mcoln1 channels restores autophagic flux and protects against I/R injury [4].
In summary, Mcoln1 is essential for regulating autophagy through its role in lysosomal ionic homeostasis. Model-based research, including studies in cancer and myocardial I/R injury, has shown that Mcoln1 is a promising target for modulating autophagy in these disease conditions. Understanding Mcoln1's function provides potential new therapeutic strategies for treating cancer and protecting against myocardial I/R injury.
References:
1. Qi, Jiansong, Xing, Yanhong, Liu, Yucheng, Guo, Feng, Wang, Wuyang. 2021. MCOLN1/TRPML1 finely controls oncogenic autophagy in cancer by mediating zinc influx. In Autophagy, 17, 4401-4422. doi:10.1080/15548627.2021.1917132. https://pubmed.ncbi.nlm.nih.gov/33890549/
2. Xing, Yanhong, Wei, Xiangqing, Liu, Yucheng, Qi, Jiansong, Wang, Wuyang. 2021. Autophagy inhibition mediated by MCOLN1/TRPML1 suppresses cancer metastasis via regulating a ROS-driven TP53/p53 pathway. In Autophagy, 18, 1932-1954. doi:10.1080/15548627.2021.2008752. https://pubmed.ncbi.nlm.nih.gov/34878954/
3. Qi, Jiansong, Li, Qingqing, Xin, Tianli, Cui, Derong, Wang, Mengmeng. 2024. MCOLN1/TRPML1 in the lysosome: a promising target for autophagy modulation in diverse diseases. In Autophagy, 20, 1712-1722. doi:10.1080/15548627.2024.2333715. https://pubmed.ncbi.nlm.nih.gov/38522082/
4. Sui, Zhongheng, Wang, Meng-Meng, Xing, Yanhong, Qi, Jiansong, Wang, Wuyang. 2022. Targeting MCOLN1/TRPML1 channels to protect against ischemia-reperfusion injury by restoring the inhibited autophagic flux in cardiomyocytes. In Autophagy, 18, 3053-3055. doi:10.1080/15548627.2022.2072657. https://pubmed.ncbi.nlm.nih.gov/35491864/
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