C57BL/6JCya-Mrtfaem1/Cya
Common Name:
Mrtfa-KO
Product ID:
S-KO-19281
Background:
C57BL/6JCya
Product Type
Age
Genotype
Sex
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Basic Information
Strain Name
Mrtfa-KO
Strain ID
KOCMP-223701-Mrtfa-B6J-VA
Gene Name
Product ID
S-KO-19281
Gene Alias
AMKL; Bsac; Mal; Mkl1; Mrtf-A
Background
C57BL/6JCya
NCBI ID
Modification
Conventional knockout
Chromosome
15
Phenotype
Document
Application
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Note: When using this mouse strain in a publication, please cite “C57BL/6JCya-Mrtfaem1/Cya mice (Catalog S-KO-19281) were purchased from Cyagen.”
Strain Description
Ensembl Number
ENSMUST00000109579
NCBI RefSeq
NM_153049
Target Region
Exon 3
Size of Effective Region
~0.8 kb
Detailed Document
Overview of Gene Research
Mrtfa, also known as Megakaryoblastic Leukemia 1 (MKL1), is a coactivator of serum response factor (SRF). SRF participates in several critical cellular functions including cell growth and apoptosis. Mrtfa couples transcriptional regulation to actin cytoskeleton dynamics, and the Mrtfa-SRF complex targets genes encoding cytoskeletal proteins and immediate early genes. It promotes the differentiation of many cell types, such as muscle and hematopoietic cells, and its interactions with other proteins broaden its cellular roles [1].
In primary hematopoietic cells, knockout of Mrtfa decreases megakaryocyte (Mk) maturation causing thrombocytopenia, while Mrtfa overexpression in HEL cells enhances megakaryopoiesis. Mrtfa increases the genomic association and activity of SRF and upregulates genes that enhance primary human megakaryopoiesis [2]. In cardiomyocytes, Cypher/ZASP deficiency leads to destabilization of F-actin, increased G-actin levels, impeding Mrtfa nuclear localisation and SRF transcription, resulting in impaired cardiomyocyte maturation [3]. In human coronary artery smooth muscle cells, Mrtfa promotes lipid accumulation, and its inhibition reduces lipid accumulation [4]. In ERα positive breast cancer cells, Mrtfa nuclear accumulation remodels ERα location and functions, shifting its activity from nuclear genome regulation to extra-nuclear non-genomic signaling [5]. In disseminated cancer cells, Mrtf activation by pericyte-like spreading is critical for metastatic colonization [6]. Genetic disruption of Mrtf-SRF interaction or an Mrtf/SRF inhibitor impacts quiescent ovarian cancer cell gene expression and induces quiescence in various cancer cells [7]. Knockdown of WAVE2 in myoblasts reduces filamentous actin levels, increases globular actin, impairs Mrtfa nuclear translocation, and suppresses myogenic differentiation [8].
In conclusion, Mrtfa plays essential roles in cell differentiation, hematopoiesis, lipid homeostasis, and cancer-related processes. Gene knockout and other functional studies in various models, especially in cells related to specific diseases like megakaryoblastic leukemia, cardiomyopathy, and cancer, have revealed its importance in these biological functions and disease conditions, providing potential therapeutic targets.
References:
1. Reed, Fiona, Larsuel, Shannon T, Mayday, Madeline Y, Scanlon, Vanessa, Krause, Diane S. 2021. MRTFA: A critical protein in normal and malignant hematopoiesis and beyond. In The Journal of biological chemistry, 296, 100543. doi:10.1016/j.jbc.2021.100543. https://pubmed.ncbi.nlm.nih.gov/33722605/
2. Rahman, Nur-Taz, Schulz, Vincent P, Wang, Lin, Esnault, Cyril, Krause, Diane S. . MRTFA augments megakaryocyte maturation by enhancing the SRF regulatory axis. In Blood advances, 2, 2691-2703. doi:10.1182/bloodadvances.2018019448. https://pubmed.ncbi.nlm.nih.gov/30337297/
3. Lyu, Jialan, Pan, Zhicheng, Li, Ruobing, Cheng, Hongqiang, Guo, Xiaogang. 2024. Cypher/ZASP drives cardiomyocyte maturation via actin-mediated MRTFA-SRF signalling. In Theranostics, 14, 4462-4480. doi:10.7150/thno.98734. https://pubmed.ncbi.nlm.nih.gov/39113806/
4. Alajbegovic, Azra, Holmberg, Johan, Daoud, Fatima, Swärd, Karl, Albinsson, Sebastian. 2021. MRTFA overexpression promotes conversion of human coronary artery smooth muscle cells into lipid-laden foam cells. In Vascular pharmacology, 138, 106837. doi:10.1016/j.vph.2021.106837. https://pubmed.ncbi.nlm.nih.gov/33516965/
5. Jehanno, Charly, Percevault, Frédéric, Boujrad, Noureddine, Métivier, Raphaël, Flouriot, Gilles. 2021. Nuclear translocation of MRTFA in MCF7 breast cancer cells shifts ERα nuclear/genomic to extra-nuclear/non genomic actions. In Molecular and cellular endocrinology, 530, 111282. doi:10.1016/j.mce.2021.111282. https://pubmed.ncbi.nlm.nih.gov/33894309/
6. Er, Ekrem Emrah, Valiente, Manuel, Ganesh, Karuna, Malladi, Srinivas, Massagué, Joan. 2018. Pericyte-like spreading by disseminated cancer cells activates YAP and MRTF for metastatic colonization. In Nature cell biology, 20, 966-978. doi:10.1038/s41556-018-0138-8. https://pubmed.ncbi.nlm.nih.gov/30038252/
7. Panesso-Gómez, Santiago, Cole, Alexander J, Wield, Alyssa, Lee, Adrian V, Buckanovich, Ronald J. 2024. Identification of the MRTFA/SRF pathway as a critical regulator of quiescence in cancer. In bioRxiv : the preprint server for biology, , . doi:10.1101/2024.11.15.623825. https://pubmed.ncbi.nlm.nih.gov/39605642/
8. Nguyen, Mai Thi, Ly, Quoc Kiet, Kim, Hyun-Jung, Lee, Wan. 2023. WAVE2 Is a Vital Regulator in Myogenic Differentiation of Progenitor Cells through the Mechanosensitive MRTFA-SRF Axis. In Cells, 13, . doi:10.3390/cells13010009. https://pubmed.ncbi.nlm.nih.gov/38201213/
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