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C57BL/6NCya-Bmal1em1flox/Cya
Common Name:
Bmal1-flox
Product ID:
S-CKO-18722
Background:
C57BL/6NCya
Product Type
Age
Genotype
Sex
Quantity
Price:
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Basic Information
Strain Name
Bmal1-flox
Strain ID
CKOCMP-11865-Bmal1-B6N-VA
Gene Name
Bmal1
Product ID
S-CKO-18722
Gene Alias
Arnt3; Arntl; BMAL1b; MOP3; bHLHe5; bmal1b'
Background
C57BL/6NCya
NCBI ID
11865
Modification
Conditional knockout
Chromosome
7
Phenotype
MGI:1096381
Document
Click here to download >>
Application
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More
Rare Disease Data Center >>
Note
Note: When using this mouse strain in a publication, please cite “C57BL/6NCya-Bmal1em1flox/Cya mice (Catalog S-CKO-18722) were purchased from Cyagen.”
Strain Description
Ensembl Number
ENSMUST00000047321
NCBI RefSeq
NM_007489
Target Region
Exon 6~8
Size of Effective Region
~2.4 kb
Detailed Document
Click here to download >>
Overview of Gene Research
Bmal1, also known as Brain and muscle arnt-like protein 1, is a crucial transcription factor in the circadian clock. It forms a heterodimer with Clock, binding to the E-box element in the promoters of genes like Per and Cry, regulating the rhythmic expression of circadian-controlled genes. It is associated with multiple biological processes, including immune regulation, metabolism, and reproduction, and thus is of great biological importance. Genetic models, such as knockout (KO) and conditional knockout (CKO) mouse models, are valuable for studying its functions [5].

In the context of disease, Bmal1 down-regulation in cardiomyocyte-specific knockout (CKB) and type 2 diabetes (T2D) mice heart accelerates cardiac hypertrophy and diastolic dysfunction in diabetic cardiomyopathy, while over-expression ameliorates these pathological changes. This occurs through Bcl2/IP3R-mediated mitochondrial Ca2 + overload [1]. Disruption of BMAL1 in mice elicits an endocrine adaption impacting insulin sensitivity and liver disease, showing a different association with fibrosis development compared to humans [2]. In sepsis-induced acute lung injury, BMAL1 deficiency in macrophages exacerbates systemic inflammation and lung injury by up-regulating CXCL2 and intensifying neutrophil-related lung injury [3]. In sepsis-induced acute kidney injury, BMAL1 over-expression alleviates renal tubular injury by reducing ferroptosis levels through inhibiting YAP expression and the Hippo pathway [4]. Bmal1 -/- mutant mice with a non-functional circadian clock show more severe and constant colitis, with disrupted daily rhythms in inflammation and epithelial proliferation [6]. In acute myeloid leukemia, knocking down BMAL1 inhibits cell growth, promotes ferroptosis, and enhances the efficacy of certain cancer drugs [7]. In glioblastoma, silencing BMAL1 promotes M1/M2 polarization through the LDHA/lactate axis, sensitizing cells to bevacizumab [8]. Also, BMAL1-KO mice are infertile, with impaired reproductive organs, gametes, and disrupted hypothalamus-pituitary-gonadal (H-P-G) axis function [9].

In conclusion, Bmal1 plays essential roles in maintaining normal physiological functions, including circadian rhythm regulation, immune homeostasis, metabolism, and reproduction. Studies using Bmal1 KO/CKO mouse models have revealed its significant contributions to various disease areas such as diabetes-related cardiomyopathy, liver diseases, sepsis-related organ injuries, colitis, leukemia, glioblastoma, and reproductive disorders. Understanding Bmal1 function provides insights into disease mechanisms and potential therapeutic targets.

References:
1. Zhang, Nannan, Yu, Hao, Liu, Tianzi, Hou, Xiaofeng, Zou, Jiangang. 2023. Bmal1 downregulation leads to diabetic cardiomyopathy by promoting Bcl2/IP3R-mediated mitochondrial Ca2+ overload. In Redox biology, 64, 102788. doi:10.1016/j.redox.2023.102788. https://pubmed.ncbi.nlm.nih.gov/37356134/
2. Jouffe, Céline, Weger, Benjamin D, Martin, Eva, Uhlenhaut, N Henriette, Gachon, Frédéric. 2022. Disruption of the circadian clock component BMAL1 elicits an endocrine adaption impacting on insulin sensitivity and liver disease. In Proceedings of the National Academy of Sciences of the United States of America, 119, e2200083119. doi:10.1073/pnas.2200083119. https://pubmed.ncbi.nlm.nih.gov/35238641/
3. Zeng, Ting, Liang, Long, Deng, Wenjun, Liu, Jing, Yang, Minghua. 2024. BMAL1 plays a crucial role in immune homeostasis during sepsis-induced acute lung injury. In Biochemical pharmacology, 226, 116379. doi:10.1016/j.bcp.2024.116379. https://pubmed.ncbi.nlm.nih.gov/38908531/
4. Yang, Songyuan, Ye, Zehua, Chen, Wu, Li, Wei, Cheng, Fan. 2024. BMAL1 alleviates sepsis-induced AKI by inhibiting ferroptosis. In International immunopharmacology, 142, 113159. doi:10.1016/j.intimp.2024.113159. https://pubmed.ncbi.nlm.nih.gov/39303541/
5. Fan, Xu-Li, Song, Ying, Qin, Dong-Xu, Lin, Pei-Yao. 2021. Regulatory Effects of Clock and Bmal1 on Circadian Rhythmic TLR Expression. In International reviews of immunology, 42, 101-112. doi:10.1080/08830185.2021.1931170. https://pubmed.ncbi.nlm.nih.gov/34544330/
6. Taleb, Zainab, Carmona-Alcocer, Vania, Stokes, Kyle, Khan, Waliul I, Karpowicz, Phillip. 2022. BMAL1 Regulates the Daily Timing of Colitis. In Frontiers in cellular and infection microbiology, 12, 773413. doi:10.3389/fcimb.2022.773413. https://pubmed.ncbi.nlm.nih.gov/35223537/
7. Zheng, Hong, Wu, Ting, Lin, Zhi, Li, Jia-Da, Yang, Minghua. 2024. Targeting BMAL1 reverses drug resistance of acute myeloid leukemia cells and promotes ferroptosis through HMGB1-GPX4 signaling pathway. In Journal of cancer research and clinical oncology, 150, 231. doi:10.1007/s00432-024-05753-y. https://pubmed.ncbi.nlm.nih.gov/38703241/
8. Wang, Fan, Liao, Wenjun, Li, Caiyan, Zhu, Ling. 2024. Silencing BMAL1 promotes M1/M2 polarization through the LDHA/lactate axis to promote GBM sensitivity to bevacizumab. In International immunopharmacology, 134, 112187. doi:10.1016/j.intimp.2024.112187. https://pubmed.ncbi.nlm.nih.gov/38733825/
9. Jiang, Yin, Li, Shiping, Xu, Wenming, Li, Jinhui, Mu, Dezhi. 2022. Critical Roles of the Circadian Transcription Factor BMAL1 in Reproductive Endocrinology and Fertility. In Frontiers in endocrinology, 13, 818272. doi:10.3389/fendo.2022.818272. https://pubmed.ncbi.nlm.nih.gov/35311235/
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
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