C57BL/6JCya-Hps4em1flox/Cya
Common Name:
Hps4-flox
Product ID:
S-CKO-18383
Background:
C57BL/6JCya
Product Type
Age
Genotype
Sex
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Basic Information
Strain Name
Hps4-flox
Strain ID
CKOCMP-192232-Hps4-B6J-VB
Gene Name
Product ID
S-CKO-18383
Gene Alias
2010205O06Rik; BLOC-3; C130020P05Rik; le; mKIAA1667
Background
C57BL/6JCya
NCBI ID
Modification
Conditional knockout
Chromosome
5
Phenotype
Document
Application
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Note: When using this mouse strain in a publication, please cite “C57BL/6JCya-Hps4em1flox/Cya mice (Catalog S-CKO-18383) were purchased from Cyagen.”
Strain Description
Ensembl Number
ENSMUST00000112359
NCBI RefSeq
NM_001359853
Target Region
Exon 5~7
Size of Effective Region
~2.3 kb
Detailed Document
Overview of Gene Research
Hps4, biogenesis of lysosome-related organelles complex 3 subunit 2, is one of the genes whose mutations are associated with Hermansky-Pudlak syndrome (HPS). Hps4 protein forms the BLOC-3 complex with HPS1, and this complex functions as a guanine nucleotide exchange factor (GEF) for RAB32/38 and as a Rab9 effector, being involved in the biogenesis of lysosome-related organelles like melanosomes [1].
In melan-le cells (an HPS4 -deficient melanocyte cell line), the hypopigmentation phenotype due to reduced tyrosinase expression and abnormal distribution, as well as reduced melanin content, can be completely rescued by re-expressing wild-type HPS4. However, the HPS4 mutant lacking Rab32/38-GEF activity fails to restore melanin content and tyrosinase trafficking, while the Rab9-binding-deficient HPS4 mutant can rescue the phenotype, indicating that activation of Rab32/38 by HPS4 is essential for melanogenesis of cultured melanocytes and Rab9 may regulate melanogenesis independently of HPS4 [1].
In plant Arabidopsis, the hps4 mutant (a new allele of SABRE) shows enhanced responses to phosphate starvation, including primary root growth inhibition, up-regulation of starvation-induced genes, and overproduction of root-associated acid phosphatases, with HPS4/SABRE antagonistically interacting with ethylene signalling [2].
In liver hepatocellular carcinoma, HPS4 was identified as an independent prognostic indicator, and knockdown of HPS4 suppressed cancer cell proliferation and induced apoptosis [3].
In two Pakistani families, a novel five-bp deletion in HPS4 led to a reading frameshift and premature termination codon in the HPS4 protein, causing typical HPS phenotypes [4].
In channel catfish, a 99-bp deletion in Hps4 at the intron 2 and exon 3 junction, resulting in exon 3 skipping, was associated with albinism [5].
In conclusion, Hps4 is crucial for the biogenesis of lysosome-related organelles, especially in melanogenesis. Its role in plant responses to phosphate starvation, as well as its potential as a prognostic indicator and therapeutic target in liver cancer, has been revealed through various genetic models. The identification of Hps4 mutations causing HPS in different populations and species further emphasizes its significance in understanding these disease conditions.
References:
1. Ohishi, Yuta, Kinoshita, Riko, Marubashi, Soujiro, Ishida, Morié, Fukuda, Mitsunori. 2019. The BLOC-3 subunit HPS4 is required for activation of Rab32/38 GTPases in melanogenesis, but its Rab9 activity is dispensable for melanogenesis. In The Journal of biological chemistry, 294, 6912-6922. doi:10.1074/jbc.RA119.007345. https://pubmed.ncbi.nlm.nih.gov/30837268/
2. Yu, Hailan, Luo, Nan, Sun, Lichao, Liu, Dong. 2012. HPS4/SABRE regulates plant responses to phosphate starvation through antagonistic interaction with ethylene signalling. In Journal of experimental botany, 63, 4527-38. doi:10.1093/jxb/ers131. https://pubmed.ncbi.nlm.nih.gov/22615140/
3. He, Ke-Jie, Nie, Zhiqiang. 2023. System analysis based on the lysosome-related genes identifies HPS4 as a novel therapy target for liver hepatocellular carcinoma. In Frontiers in oncology, 13, 1221498. doi:10.3389/fonc.2023.1221498. https://pubmed.ncbi.nlm.nih.gov/37781184/
4. Zaman, Qaiser, Anas, Muhammad, Rehman, Gauhar, Jelani, Musharraf, Naseer, Muhammad Imran. 2023. Report of Hermansky-Pudlak Syndrome in Two Families with Novel Variants in HPS3 and HPS4 Genes. In Genes, 14, . doi:10.3390/genes14010145. https://pubmed.ncbi.nlm.nih.gov/36672886/
5. Li, Yueru, Geng, Xin, Bao, Lisui, Dunham, Rex, Liu, Zhanjiang. 2017. A deletion in the Hermansky-Pudlak syndrome 4 (Hps4) gene appears to be responsible for albinism in channel catfish. In Molecular genetics and genomics : MGG, 292, 663-670. doi:10.1007/s00438-017-1302-8. https://pubmed.ncbi.nlm.nih.gov/28289846/
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