C57BL/6JCya-Alas1em1/Cya
Common Name:
Alas1-KO
Product ID:
S-KO-17292
Background:
C57BL/6JCya
Product Type
Age
Genotype
Sex
Quantity
Price:
Contact for Pricing
Basic Information
Strain Name
Alas1-KO
Strain ID
KOCMP-11655-Alas1-B6J-VA
Gene Name
Product ID
S-KO-17292
Gene Alias
ALAS; ALAS-N; Alas-1; Alas-h
Background
C57BL/6JCya
NCBI ID
Modification
Conventional knockout
Chromosome
9
Phenotype
Document
Application
--
Note: When using this mouse strain in a publication, please cite “C57BL/6JCya-Alas1em1/Cya mice (Catalog S-KO-17292) were purchased from Cyagen.”
Strain Description
Ensembl Number
ENSMUST00000141118
NCBI RefSeq
NM_020559
Target Region
Exon 6
Size of Effective Region
~0.2 kb
Detailed Document
Overview of Gene Research
Alas1, also known as 5'-aminolevulinate synthase 1, is the rate-limiting enzyme in heme synthesis pathway [1,2,4]. Heme is crucial for numerous biological processes, such as oxygen transport, electron transfer, and enzyme catalysis. Thus, Alas1 is of great biological importance as it maintains intracellular heme levels [2].
In zebrafish, Alas1-deficient models showed proper neutrophil initiation, but blocked neutrophil maturation due to heme deficiency, with lipid storage and granule formation deficiencies, and loss of heme-dependent granule protein activities. Consequently, these zebrafish had impaired bactericidal ability and augmented inflammatory responses when challenged with Escherichia coli, demonstrating the role of Alas1 in neutrophil maturation and physiological function [3]. In mice, heterozygous disruption of Alas1 led to an accelerated age-dependent reduction in free heme, but not total heme, in skeletal muscle and liver, which could account for a prediabetic phenotype and mitochondrial abnormality [5]. In cultured cardiomyocytes, decreasing Alas1 abundance by doxorubicin disrupted heme synthesis, impaired iron utilization, resulting in iron overload and ferroptosis, while Alas1 overexpression prevented this outcome. Also, administration of 5-aminolevulinic acid (5-ALA), the product of Alas1, to cultured cardiomyocytes and mice suppressed iron overload and lipid peroxidation, preventing doxorubicin-induced ferroptosis and cardiomyopathy [1]. In colorectal cancer cells, suppressing Alas1 inhibited cell proliferation and metastasis, suggesting its potential as a therapeutic target [4].
In conclusion, Alas1 is essential for heme synthesis, which is involved in multiple biological processes. Studies using gene-deficient models in zebrafish and mice, as well as in vitro cell studies, have revealed its role in neutrophil maturation, age-related heme changes, cardiotoxicity-related ferroptosis, and colorectal cancer progression. These findings provide insights into the underlying mechanisms of related diseases and potential therapeutic directions.
References:
1. Abe, Ko, Ikeda, Masataka, Ide, Tomomi, Imai, Hirotaka, Tsutsui, Hiroyuki. 2022. Doxorubicin causes ferroptosis and cardiotoxicity by intercalating into mitochondrial DNA and disrupting Alas1-dependent heme synthesis. In Science signaling, 15, eabn8017. doi:10.1126/scisignal.abn8017. https://pubmed.ncbi.nlm.nih.gov/36318618/
2. Li, Wentao, Li, Kunyu, He, Xiaoyun, Liu, Yufang, Chu, Mingxing. 2023. ALAS1 associated with goat kidding number trait was regulated by the transcription factor ASCL2 to affect granulosa cell proliferation. In Animal genetics, 54, 189-198. doi:10.1111/age.13287. https://pubmed.ncbi.nlm.nih.gov/36632647/
3. Lian, Junwei, Chen, Jiakui, Wang, Kun, Zhang, Wenqing, Zhang, Yiyue. 2018. Alas1 is essential for neutrophil maturation in zebrafish. In Haematologica, 103, 1785-1795. doi:10.3324/haematol.2018.194316. https://pubmed.ncbi.nlm.nih.gov/29954941/
4. Zhao, Yalei, Zhang, Xiaoyun, Liu, Yabin, Han, Mei, Li, Binghui. . Inhibition of ALAS1 activity exerts anti-tumour effects on colorectal cancer in vitro. In Saudi journal of gastroenterology : official journal of the Saudi Gastroenterology Association, 26, 144-152. doi:10.4103/sjg.SJG_477_19. https://pubmed.ncbi.nlm.nih.gov/32270771/
5. van Wijk, Koen, Akabane, Takeru, Kimura, Tomohiro, Nakajima, Motowo, Nakajima, Osamu. 2020. Heterozygous disruption of ALAS1 in mice causes an accelerated age-dependent reduction in free heme, but not total heme, in skeletal muscle and liver. In Archives of biochemistry and biophysics, 697, 108721. doi:10.1016/j.abb.2020.108721. https://pubmed.ncbi.nlm.nih.gov/33307066/
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