PRMT1 Mouse
Description
Definition and Genetic Engineering of PRMT1 Mouse Models
PRMT1 mouse models include conditional knockouts (cKO), tissue-specific deletions, and transgenic strains. These models often employ Cre-lox systems to target PRMT1 in specific cell types or developmental stages:
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PRMT1<sup>f/f</sup>/Mx1-Cre: Inducible deletion in adult hematopoietic cells via polyinosinic-polycytidylic acid (pIpC) injections .
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Pf4-PRMT1: Transgenic mice expressing human PRMT1 under the platelet factor 4 promoter to study megakaryocyte biology .
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Stra8-GFPCre and Zp3-Cre: Germline-specific deletions to explore spermatogonial homeostasis .
Hematopoiesis and Stem Cell Function
PRMT1 is essential for hematopoietic stem and progenitor cell (HSPC) maintenance and differentiation:
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PRMT1 deletion disrupts erythroid maturation, leading to accumulation of primitive erythroblasts (S0/S1 populations) and reduced Ter119<sup>+</sup> cells .
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Loss of PRMT1 reduces short-term hematopoietic stem cells (ST-HSCs) and granulocyte-macrophage progenitors (GMPs) .
Bone Metabolism and Osteoclastogenesis
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PRMT1<sup>+/−</sup> Mice: Haploinsufficiency protects against ovariectomy-induced bone loss, with reduced osteoclast activity and tartrate-resistant acid phosphatase (TRAP) levels .
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Mechanism: PRMT1 interacts with NF-κB to enhance transcription of osteoclastogenesis genes (e.g., TRAP, CTSK) .
Craniofacial Development
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Palate Formation: PRMT1 regulates MSX1 phase separation via methylation, a process critical for embryonic palatal fusion. Inhibiting PRMT1 disrupts MSX1 condensate dynamics, leading to cleft palate in mice .
Germline and Fertility
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Prmt1-sKO Mice (Stra8-GFPCre): Exhibit spermatogonial depletion and male infertility due to defective arginine methylome regulation .
Molecular Mechanisms and Pathways
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Substrate Methylation: PRMT1 methylates histones (H4R3me2a), transcription factors (RUNX1, NF-κB), and RNA-binding proteins (RBM15) .
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Downstream Effects:
Therapeutic Implications
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Cancer: PRMT1 overexpression in leukemias and solid tumors correlates with poor prognosis .
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Osteoporosis: PRMT1 inhibitors (e.g., MS023, DB75) reduce osteoclast activity and bone resorption .
Table 1: Hematopoietic Defects in PRMT1 cKO Mice
| Parameter | PRMT1 cKO vs. Wild-Type | Citation |
|---|---|---|
| RBC Count | ↓ 30% | |
| Bone Marrow LSK Cells | No change | |
| ST-HSC Frequency | ↓ 50% | |
| Megakaryocyte Clusters | Increased |
Table 2: PRMT1 in Disease Models
Product Specs
VNKDKPLGAV ALKSYEEELA KDPRIAATME NAQKGEIMPN IPQMSAFWYA VRTAVINAAS GRQTVDEALK DAQTNSSSNN NNNNNNNNLG IEGRGSHMAA AEAANCIMEV SCGQAESSEK PNAEDMTSKD YYFDSYAHFG IHEEMLKDEV RTLTYRNSMF HNRHLFKDKV VLDVGSGTGILCMFAAKAGA RKVIGIECSS ISDYAVKIVK ANKLDHVVTI IKGKVEEVEL PVEKVDIIIS EWMGYCLFYE SMLNTVLHAR DKWLAPDGLI FPDRATLYVT AIEDRQYKDY KIHWWENVYG
FDMSCIKDVA IKEPLVDVVD PKQLVTNACL IKEVDIYTVK VEDLTFTSPF CLQVKRNDYVHALVAYFNIE FTRCHKRTGF STSPESPYTH WKQTVFYMED YLTVKTGEEI FGTIGMRPNA KNNRDLDFTI DLDFKGQLCE LSCSTDYRMR.
Q&A
Basic Research Questions
What essential biological processes require PRMT1 in mouse models?
PRMT1 is critical for:
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Spermatogenesis: Prmt1 KO mice exhibit meiotic arrest at the zygotene-like stage due to unresolved DNA double-strand breaks (DSBs) .
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B cell differentiation: PRMT1 deficiency reduces germinal center (GC) expansion and high-affinity antibody responses by impairing GC B cell (GCBC) dynamics .
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Palate development: PRMT1-mediated methylation of MSX1 regulates phase separation, with defects leading to cleft palate .
What are standard methodologies for studying PRMT1 in mice?
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Conditional knockout models: Use tissue-specific Cre drivers (e.g., Cγ1-cre for B cells) .
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Inhibitor studies: MS023 (type I PRMT inhibitor) reduces asymmetric dimethylarginine (aDMA) levels in activated B cells .
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Phenotypic assays: Histology for GC structures , FRAP for protein condensate dynamics , and γH2AX staining for DSBs .
How does PRMT1 deficiency affect DNA repair in mouse cells?
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PRMT1-null mouse embryonic fibroblasts (MEFs) show:
Advanced Research Questions
How do PRMT1 splice variants influence substrate specificity in murine systems?
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Human PRMT1 has splice variants with distinct substrate preferences (e.g., altered N-terminal regions) .
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Methodological consideration: Compare isoform-specific activity using in vitro methylation assays with substrates like MRE11 or MSX1 .
What explains contradictory findings on PRMT1’s role in B cell proliferation?
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Discrepancies arise from:
How does PRMT1 regulate phase separation in craniofacial development?
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PRMT1 dimethylates MSX1 at arginine residues, enabling dynamic nuclear condensates .
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Experimental approach:
Methodological Challenges and Solutions
How to address partial lethality in constitutive PRMT1 KO models?
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Strategy: Use conditional alleles (e.g., Prmt1<sup>FL/−</sup>) or inducible Cre systems.
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Validation: Monitor aDMA levels via immunoblotting with pan-aDMA antibodies .
What controls are critical when assessing PRMT1’s role in meiosis?
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Essential controls:
Data Contradictions and Interpretation
Why do PRMT1 inhibitors show cell type-specific effects in vivo?
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Key factors:
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Recommendation: Profile aDMA targets via mass spectrometry in target tissues.
How to reconcile PRMT1’s dual roles in promoting and suppressing tumorigenesis?
Product Science Overview
Protein Arginine Methyltransferase 1 (PRMT1) is a member of the protein arginine methyltransferase family, which plays a crucial role in the post-translational modification of proteins. PRMT1 is the predominant arginine methyltransferase in mammals, responsible for more than 85% of the arginine methylation activity in cells . This enzyme is involved in various cellular processes, including transcriptional regulation, RNA processing, DNA repair, and signal transduction .
PRMT1 catalyzes the transfer of methyl groups from S-adenosylmethionine (AdoMet) to the guanidine nitrogen atoms of arginine residues in target proteins, forming monomethylarginine and asymmetric dimethylarginine . This methylation process increases the structural diversity of proteins and modulates their function within the cell .
PRMT1 is a type-I methyltransferase that specifically targets histone H4 in eukaryotic cells, altering its structure and enabling chromatin remodeling . This modification is essential for the regulation of gene expression and maintenance of genomic integrity .
PRMT1 is critical for various biological processes, including:
- Transcriptional Regulation: PRMT1 acts as a transcriptional co-activator by methylating histones and other transcription factors, thereby influencing gene expression .
- RNA Processing: PRMT1 is involved in the regulation of RNA splicing and processing by methylating RNA-binding proteins .
- DNA Repair: PRMT1 plays a role in the DNA damage response by methylating proteins involved in DNA repair pathways .
- Signal Transduction: PRMT1 modulates signal transduction pathways by methylating signaling proteins .
In mouse models, PRMT1 has been shown to regulate various physiological processes. For instance, PRMT1 is essential for the development and homeostasis of enteroendocrine cells in the adult intestinal epithelium . Enteroendocrine cells are hormone-producing cells that play a crucial role in energy homeostasis and metabolism . PRMT1 deficiency in mice leads to an increase in the number of enteroendocrine cells and upregulation of enteroendocrine-specific hormones and transcription factors .
