C57BL/6JCya-Pld4em1/Cya
Common Name
Pld4-KO
Product ID
S-KO-17290
Backgroud
C57BL/6JCya
Strain ID
KOCMP-104759-Pld4-B6J-VB
Status
When using this mouse strain in a publication, please cite “Pld4-KO Mouse (Catalog S-KO-17290) were purchased from Cyagen.”
Product Type
Age
Genotype
Sex
Quantity
The standard delivery applies for a guaranteed minimum of three heterozygous carriers. Breeding services for homozygous carriers and/or specified sex are available.
Basic Information
Strain Name
Pld4-KO
Strain ID
KOCMP-104759-Pld4-B6J-VB
Gene Name
Product ID
S-KO-17290
Gene Alias
thss
Background
C57BL/6JCya
Gene Full Name
phospholipase D family, member 4
Modification
Conventional knockout
NCBI ID
Phenotype
Chromosome
Chr 12 (Mouse)
Application
--
Datasheet
Strain Description
Ensembl Transcript ID
ENSMUST00000063888
NCBI Transcript ID
NM_178911
Target Region
Exon 6
Size of Effective Region
~1.0 kb
Overview of Gene Research
Pld4, or Phospholipase D4, is an enzyme involved in multiple biological processes. It is an endolysosomal exonuclease of ssDNA and ssRNA, regulating innate immunity [3,4,6,7]. It also participates in the synthesis of lysosomal S,S-Bis(monoacylglycero)phosphate (S,S-BMP), a crucial phospholipid for lipid degradation in lysosomes, especially for gangliosides [1,2].
Deletion of Pld4 in murine tissues (spleen) significantly reduced S,S-BMP levels, leading to gangliosidosis and lysosomal abnormalities [1,2]. Pld4 -/- mice accumulate small ssRNAs and develop spontaneous fatal hemophagocytic lymphohistiocytosis (HLH) characterized by inflammatory liver damage and overproduction of Interferon (IFN)-γ, suggesting its role in regulating nucleic acid sensing pathways [3]. In addition, Pld4 mutant mice showed autoimmune phenotypes similar to systemic lupus erythematosus (SLE), including splenomegaly, lymphadenopathy, and autoantibody production, indicating its involvement in SLE-related processes [5].
In conclusion, Pld4 is essential for lipid degradation in lysosomes and regulation of innate immunity. The gene knockout mouse models have revealed its role in diseases such as gangliosidosis, HLH, and SLE, highlighting its importance in understanding the pathogenesis of these diseases and potentially guiding the development of new therapeutic strategies.
References：
1. Singh, Shubham, Dransfeld, Ulrich E, Ambaw, Yohannes A, Farese, Robert V, Walther, Tobias C. 2024. PLD3 and PLD4 synthesize S,S-BMP, a key phospholipid enabling lipid degradation in lysosomes. In Cell, 187, 6820-6834.e24. doi:10.1016/j.cell.2024.09.036. https://pubmed.ncbi.nlm.nih.gov/39423811/
2. Singh, Shubham, Dransfeld, Ulrich, Ambaw, Yohannes, Farese, Robert V, Walther, Tobias C. 2024. PLD3 and PLD4 synthesize S,S-BMP, a key phospholipid enabling lipid degradation in lysosomes. In bioRxiv : the preprint server for biology, , . doi:10.1101/2024.03.21.586175. https://pubmed.ncbi.nlm.nih.gov/38562702/
3. Gavin, Amanda L, Huang, Deli, Blane, Tanya R, Miyake, Kensuke, Nemazee, David. 2021. Cleavage of DNA and RNA by PLD3 and PLD4 limits autoinflammatory triggering by multiple sensors. In Nature communications, 12, 5874. doi:10.1038/s41467-021-26150-w. https://pubmed.ncbi.nlm.nih.gov/34620855/
4. Lee, Jinny Claire, Shirey, Ryan J, Turner, Lewis D, Lairson, Luke L, Janda, Kim D. 2024. Discovery of PLD4 modulators by high-throughput screening and kinetic analysis. In Results in chemistry, 7, . doi:10.1016/j.rechem.2024.101349. https://pubmed.ncbi.nlm.nih.gov/38560090/
5. Akizuki, Shuji, Ishigaki, Kazuyoshi, Kochi, Yuta, Mimori, Tsuneyo, Terao, Chikashi. 2019. PLD4 is a genetic determinant to systemic lupus erythematosus and involved in murine autoimmune phenotypes. In Annals of the rheumatic diseases, 78, 509-518. doi:10.1136/annrheumdis-2018-214116. https://pubmed.ncbi.nlm.nih.gov/30679154/
6. Yuan, Meng, Peng, Linghang, Huang, Deli, Wilson, Ian A, Nemazee, David. 2024. Structural and mechanistic insights into disease-associated endolysosomal exonucleases PLD3 and PLD4. In Structure (London, England : 1993), 32, 766-779.e7. doi:10.1016/j.str.2024.02.019. https://pubmed.ncbi.nlm.nih.gov/38537643/
7. Shirey, Ryan J, Turner, Lewis D, Lairson, Luke L, Janda, Kim D. 2021. Modulators of immunoregulatory exonucleases PLD3 and PLD4 identified by high-throughput screen. In Bioorganic & medicinal chemistry letters, 49, 128293. doi:10.1016/j.bmcl.2021.128293. https://pubmed.ncbi.nlm.nih.gov/34332037/
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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