Alpl KO Mouse
製品名
Alpl KO Mouse
製品ID
C001849
系統名
C57BL/6JCya-Alplem1/Cya
背景情報
C57BL/6JCya
状況
このマウス系統を論文で使用する場合は、「Alpl KO Mouse（カタログ番号C001849）はサイアジェンから購入しました。」と引用してください。
製品タイプ
年齢
遺伝子型
性別
数量
遺伝子名
遺伝子別名
ALP, Akp2, TNAP, Akp-2, APTNAP, TNSALP
NCBI ID
染色体
Chr 4
MGI ID
さらに
系統詳細
The ALPL gene encodes for the tissue-nonspecific alkaline phosphatase (TNSALP) enzyme, a membrane-bound glycoprotein. This enzyme is expressed in a variety of cellular tissues, most notably in the liver, bone, and kidney, as well as in other areas like teeth and mesenchymal stem cells [1]. Its primary function is to act as a hydrolase, removing phosphate groups from molecules. This is a critical function for skeletal and dental mineralization, where it hydrolyzes inorganic pyrophosphate (a mineralization inhibitor) into phosphate, which then combines with calcium to form bone [2]. Mutations in the ALPL gene lead to hypophosphatasia (HPP), a rare inherited metabolic disease characterized by defective bone and tooth mineralization, rickets, osteomalacia, and in severe cases, seizures and respiratory complications. The severity of HPP varies, ranging from mild forms with dental issues to life-threatening perinatal forms [3]. Variations in the ALPL gene may also be associated with other diseases, such as osteoporosis. Research has found a high frequency of homozygous common ALPL gene variants in adult patients with atypical femoral fractures or with biochemical/clinical signs of hypophosphatasia (HPP). This suggests that variations in the ALPL gene may be linked to an increased risk of these fractures [4]. Furthermore, the expression and function of the ALPL gene may be relevant to cancer immunotherapy. Studies have shown that an alkaline phosphatase isoform, known as ALPL-1, is highly expressed in osteosarcoma (OS) [5].
The Alpl KO mouse is a knockout (KO) model in which the exon 3~4 of the Alpl gene (homologous to the human ALPL gene) has been deleted via gene-editing technology. Preliminary validation data indicate that homozygous Alpl KO mice have a short lifespan, dying within four weeks when given a specialized diet. If they are not provided with this dietary support, no surviving homozygous individuals are obtained. This model can be used to study the pathogenic mechanisms of diseases such as hypophosphatasia (HPP), osteoporosis, and osteosarcoma (OS), and to provide a basis for developing related therapeutic strategies.
参考文献
Sato M, Saitoh I, Kiyokawa Y, Iwase Y, Kubota N, Ibano N, Noguchi H, Yamasaki Y, Inada E. Tissue-Nonspecific Alkaline Phosphatase, a Possible Mediator of Cell Maturation: Towards a New Paradigm. Cells. 2021 Nov 28;10(12):3338.
Alonso N, Larraz-Prieto B, Berg K, Lambert Z, Redmond P, Harris SE, Deary IJ, Pugh C, Prendergast J, Ralston SH. Loss-of-Function Mutations in the ALPL Gene Presenting with Adult Onset Osteoporosis and Low Serum Concentrations of Total Alkaline Phosphatase. J Bone Miner Res. 2020 Apr;35(4):657-661.
Villa-Suárez JM, García-Fontana C, Andújar-Vera F, González-Salvatierra S, de Haro-Muñoz T, Contreras-Bolívar V, García-Fontana B, Muñoz-Torres M. Hypophosphatasia: A Unique Disorder of Bone Mineralization. Int J Mol Sci. 2021 Apr 21;22(9):4303.
Marini F, Masi L, Giusti F, Cianferotti L, Cioppi F, Marcucci G, Ciuffi S, Biver E, Toro G, Iolascon G, Iantomasi T, Brandi ML. ALPL Genotypes in Patients With Atypical Femur Fractures or Other Biochemical and Clinical Signs of Hypophosphatasia. J Clin Endocrinol Metab. 2022 Apr 19;107(5):e2087-e2094.
Mensali N, Köksal H, Joaquina S, Wernhoff P, Casey NP, Romecin P, Panisello C, Rodriguez R, Vimeux L, Juzeniene A, Myhre MR, Fåne A, Ramírez CC, Maggadottir SM, Duru AD, Georgoudaki AM, Grad I, Maturana AD, Gaudernack G, Kvalheim G, Carcaboso AM, de Alava E, Donnadieu E, Bruland ØS, Menendez P, Inderberg EM, Wälchli S. ALPL-1 is a target for chimeric antigen receptor therapy in osteosarcoma. Nat Commun. 2023 Jun 8;14(1):3375.
系統作製戦略
The mouse Alpl gene consists of twelve exons, with the ATG start codon located in exon 2 and the TGA stop codon in exon 12. In this strain, the region of exons 3~4 was deleted using gene-editing technology.
Figure 1. Diagram of the gene editing strategy for the generation of Alpl KO mice.
適用分野
Research on hypophosphatasia (HPP);
Research on osteoporosis;
Research on osteosarcoma (OS).
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