C57BL/6JCya-Pdzd8em1flox/Cya
Common Name:
Pdzd8-flox
Product ID:
S-CKO-00563
Background:
C57BL/6JCya
Product Type
Age
Genotype
Sex
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Basic Information
Strain Name
Pdzd8-flox
Strain ID
CKOCMP-107368-Pdzd8-B6J-VA
Gene Name
Product ID
S-CKO-00563
Gene Alias
A630041P07Rik; Pdzk8
Background
C57BL/6JCya
NCBI ID
Modification
Conditional knockout
Chromosome
19
Phenotype
Document
Application
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Note: When using this mouse strain in a publication, please cite “C57BL/6JCya-Pdzd8em1flox/Cya mice (Catalog S-CKO-00563) were purchased from Cyagen.”
Strain Description
Ensembl Number
ENSMUST00000099274
NCBI RefSeq
NM_001033222
Target Region
Exon 3
Size of Effective Region
~1.0 kb
Detailed Document
Overview of Gene Research
PDZD8, the protein encoded by the PDZ domain containing 8 gene, has multiple essential functions. It acts as a tethering protein at the interfaces of different organelles, such as between the endoplasmic reticulum (ER) and mitochondria, ER and late endosome/lysosome, which is crucial for processes like Ca²⁺ dynamics regulation, lipid transfer, and organelle contact formation [2,3,4,6]. It is also involved in metabolic adaptation pathways, with the AMPK-PDZD8-GLS1 axis promoting glutaminolysis during glucose shortage [1].
In mouse models, PDZD8-KO mice show abnormal accumulation of cholesteryl esters in the brain due to impaired lipophagy, leading to growth retardation and behavioral abnormalities related to emotion, cognition, and adaptation [5]. In humans, homozygous premature termination codons in PDZD8 are associated with syndromic intellectual disability with autistic features. Similar cognitive deficits are replicated in Drosophila with knockdown of the PDZD8 ortholog and in Pdzd8 homozygous mutant mice, suggesting a conserved role in cognitive function [7]. In stress-induced hypertension rat models, reduced PDZD8 expression in the rostral ventrolateral medulla disrupts ER-mitochondria associations and mitochondrial functions, contributing to the disease pathology [8].
In summary, PDZD8 is vital for organelle-organelle interactions, lipid metabolism, and metabolic adaptation. Studies using gene knockout models in mice, flies, and rats have revealed its significance in cognitive development, emotional regulation, and blood pressure control, providing insights into the pathophysiology of related diseases.
References:
1. Li, Mengqi, Wang, Yu, Wei, Xiaoyan, Zhang, Chen-Song, Lin, Sheng-Cai. 2024. AMPK targets PDZD8 to trigger carbon source shift from glucose to glutamine. In Cell research, 34, 683-706. doi:10.1038/s41422-024-00985-6. https://pubmed.ncbi.nlm.nih.gov/38898113/
2. Hirabayashi, Yusuke, Kwon, Seok-Kyu, Paek, Hunki, Pon, Liza A, Polleux, Franck. . ER-mitochondria tethering by PDZD8 regulates Ca2+ dynamics in mammalian neurons. In Science (New York, N.Y.), 358, 623-630. doi:10.1126/science.aan6009. https://pubmed.ncbi.nlm.nih.gov/29097544/
3. Nakamura, Koki, Aoyama-Ishiwatari, Saeko, Nagao, Takahiro, Polleux, Franck, Hirabayashi, Yusuke. 2024. PDZD8-FKBP8 tethering complex at ER-mitochondria contact sites regulates mitochondrial complexity. In bioRxiv : the preprint server for biology, , . doi:10.1101/2023.08.22.554218. https://pubmed.ncbi.nlm.nih.gov/38895210/
4. Thakur, Rajan S, O'Connor-Giles, Kate M. 2023. PDZD8 promotes autophagy at ER-Lysosome contact sites to regulate synaptogenesis. In bioRxiv : the preprint server for biology, , . doi:10.1101/2023.10.30.564828. https://pubmed.ncbi.nlm.nih.gov/37961523/
5. Kurihara, Yuji, Mitsunari, Kotone, Mukae, Nagi, Miyakawa, Tsuyoshi, Shirane, Michiko. 2023. PDZD8-deficient mice manifest behavioral abnormalities related to emotion, cognition, and adaptation due to dyslipidemia in the brain. In Molecular brain, 16, 11. doi:10.1186/s13041-023-01002-4. https://pubmed.ncbi.nlm.nih.gov/36658656/
6. Gao, Yuan, Xiong, Juan, Chu, Qing-Zhu, Ji, Wei-Ke. 2021. PDZD8-mediated lipid transfer at contacts between the ER and late endosomes/lysosomes is required for neurite outgrowth. In Journal of cell science, 135, . doi:10.1242/jcs.255026. https://pubmed.ncbi.nlm.nih.gov/33912962/
7. Al-Amri, Ahmed H, Armstrong, Paul, Amici, Mascia, Inglehearn, Chris F, Clapcote, Steven J. 2022. PDZD8 Disruption Causes Cognitive Impairment in Humans, Mice, and Fruit Flies. In Biological psychiatry, 92, 323-334. doi:10.1016/j.biopsych.2021.12.017. https://pubmed.ncbi.nlm.nih.gov/35227461/
8. Liu, Tianfeng, Wang, Linping, Chen, Gaojun, Zhang, Shuai, Du, Dongshu. 2023. PDZD8-mediated endoplasmic reticulum-mitochondria associations regulate sympathetic drive and blood pressure through the intervention of neuronal mitochondrial homeostasis in stress-induced hypertension. In Neurobiology of disease, 183, 106173. doi:10.1016/j.nbd.2023.106173. https://pubmed.ncbi.nlm.nih.gov/37247681/
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