Name: huCD98HC(SLC3A2) Mouse
Brand: サイヤジェン（Cyagen）
SKU: C001857

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huCD98HC(SLC3A2) Mouse

製品名

huCD98HC(SLC3A2) Mouse

製品ID

C001857

系統名

C57BL/6NCya-Slc3a2^tm1(hSLC3A2)/Cya

背景情報

C57BL/6NCya

状況

このマウス系統を論文で使用する場合は、「huCD98HC(SLC3A2) Mouse（カタログ番号C001857）はサイアジェンから購入しました。」と引用してください。

HUGO-GT Humanized Models

Immune Target Humanized Mouse Models

Blood-Brain Barrier

製品タイプ

年齢

遺伝子型

性別

数量

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HUGO-GT Humanized Models

Immune Target Humanized Mouse Models

Blood-Brain Barrier

基本情報

検証 Data

系統詳細

The SLC3A2 gene (Solute Carrier Family 3 Member 2), also known as CD98hc or 4F2hc, is ubiquitously expressed across many tissues and is often upregulated in various cancers, including lung, breast, and colorectal cancer. It encodes the cell-surface, transmembrane heavy chain of a heterodimeric amino acid transporter complex, which is covalently bound via disulfide bonds to a light chain from the SLC7A family (e.g., SLC7A5/LAT1 or SLC7A11/xCT). The primary function of the encoded protein is to act as a chaperone necessary for the light chain's proper plasma membrane localization and stability. The resulting functional complex transports specific essential amino acids; for instance, the SLC3A2/SLC7A5 dimer transports L-type neutral amino acids, while the SLC3A2/SLC7A7 dimer transports dibasic amino acids. This nutrient uptake is crucial for cell growth and metabolic reprogramming^[1]. Beyond its transport role, SLC3A2 independently modulates integrin-dependent signaling pathways, affecting processes like cell spreading, adhesion, migration, and proliferation, which links it closely to cancer progression^[2]. Cellular tissues with notable expression include trophoblasts (placenta), kidney proximal tubular cells, glandular cells (breast), Sertoli cells (testis), and various immune cells. SLC3A2 is primarily associated with cancer, where it acts as an oncoprotein and prognostic marker. It is also involved in specific cell death pathways like disulfidptosis^[3]. Genetic associations have also been suggested between the SLC3A2 locus and conditions like schizophrenia, vitiligo, and Ulcerative Colitis, highlighting its broader role in cellular homeostasis^[4].

huCD98HC(SLC3A2) mouse is a humanized model generated using gene editing technology, in which the mouse Slc3a2 endogenous extracellular domain is replaced with the human SLC3A2 extracellular domain. The murine cytoplasmic domain and transmembrane domain are preserved. This model can be used for research related to cancer, amino acid transport and metabolic intervention, immune regulation and autoimmunity, as well as the development of SLC3A2-targeted drugs.

参考文献

Xia P, Dubrovska A. CD98 heavy chain as a prognostic biomarker and target for cancer treatment. Front Oncol. 2023 Sep 26;13:1251100.

Li Z, Chen S, He X, Gong S, Sun L, Weng L. SLC3A2 promotes tumor-associated macrophage polarization through metabolic reprogramming in lung cancer. Cancer Sci. 2023 Jun;114(6):2306-2317.

Zhang X, Lin Y, Shi L, Zhai A, Wu C, Zhu QY. Disulfidptosis-related gene SLC3A2: a novel prognostic biomarker in nasopharyngeal carcinoma and head and neck squamous cell carcinoma. Front Oncol. 2025 Jan 24;15:1451034.

Yang QQ, Guo JA, Zhang K, Li SH, Xia WY, Wang DX, Xie LS, Wang JM, Wu QF. Disulfidptosis and Its Hub Gene Slc3a2 Involved in Ulcerative Colitis Pathogenesis, Disease Progression, and Patient Responses to Biologic Therapies. Int J Mol Sci. 2024 Dec 17;25(24):13506.

系統作製戦略

The mouse Slc3a2 endogenous extracellular domain was replaced with the human SLC3A2 extracellular domain. The murine cytoplasmic domain and transmembrane domain were preserved.

Figure 1. Gene editing strategy of huCD98HC(SLC3A2) mice.

適用分野

Screening, development, and preclinical evaluation of CD98HC(SLC3A2)-targeted drugs;

Research on the pathological mechanisms and therapeutic approaches of various cancers;

Research on amino acid transport mechanisms and metabolic diseases;

Research on immune regulation and autoimmunity;

Research and evaluation of drug delivery across the blood-brain barrier (BBB).

検証 Data

1. Gene Expression

The transcription levels of human SLC3A2 (hSLC3A2) and mouse Slc3a2 (mSlc3a2) were analyzed in huCD98HC(SLC3A2) mice by RT-qPCR. Specific primers were used to detect hSLC3A2 and mSlc3a2 transcripts in the cerebral cortex, hippocampus, spinal cord, kidney, and liver tissues collected from huCD98HC(SLC3A2) mice and wild-type (WT) mice. Mouse Gapdh was used as the internal reference gene, and the relative expression levels of hSLC3A2 and mSlc3a2 in each tissue were calculated. Data are presented as mean ± SEM. The results showed that hSLC3A2 transcripts were detected in multiple tissues of huCD98HC(SLC3A2) mice, whereas mSlc3a2 transcripts were not detected. In contrast, mSlc3a2 transcripts were detected in multiple tissues of WT mice, while hSLC3A2 transcripts were not detected.

Figure 2. Gene expression analysis in the cerebral cortex, hippocampus, spinal cord, kidney, and liver tissues of huCD98HC(SLC3A2) and wild-type (WT) mice (7 weeks old, both sexes, homozygous, n=3).

2. Protein Expression

（1）Western Blot

The results showed that human CD98HC protein was detected in the cerebral cortex, hippocampus, spinal cord, small intestine, and spleen of homozygous huCD98HC(SLC3A2) mice, whereas it was not detected in the tissues of wild-type (WT) mice.

Figure 3. Human CD98HC protein expression in the cerebral cortex, hippocampus, spinal cord, small intestine, and spleen of huCD98HC(SLC3A2) and wild-type (WT) mice (7 weeks old, homozygous, male, n=2).

（2）Flow Cytometric Analysis

(A-B) Representative histograms (A) and statistical plots of median fluorescence intensity (MFI) (B) of PE-mCD98hc on monocytes in the blood and bone marrow of WT and huCD98HC(SLC3A2) mice.

(C-D) Representative histograms (C) and statistical plots of MFI (D) of FITC-hCD98hc on monocytes in the blood and bone marrow of WT and huCD98HC(SLC3A2) mice.

Data are presented as mean ± standard error of the mean (mean ± SEM). Statistical analysis was performed using a two-tailed unpaired t-test; **p < 0.01, ***p < 0.001.

The results showed that monocytes in multiple tissues of WT mice highly expressed mCD98hc, with low-level signal of hCD98hc; in contrast, monocytes in multiple tissues of huCD98HC(SLC3A2) mice highly expressed hCD98hc, and the MFI of hCD98hc was significantly higher than that in WT mice. These results indicate that huCD98HC(SLC3A2) mice successfully express hCD98hc protein but not mCD98hc protein.

Figure 4. Flow cytometric analysis of CD98hc protein expression in peripheral blood monocytes of huCD98HC(SLC3A2) mice (7 weeks old, male, n=3).

（3）Immunofluorescence (IF) co-staining

IF colocalization staining revealed that human CD98hc (red) and the endothelial marker mCD31 (green) colocalize in the brain microvascular endothelial cells of 6-week-old female huCD98HC(SLC3A2) mice. Nuclei were counterstained with DAPI (blue). White triangles indicate colocalization signals of human CD98hc and mCD31. Scale bar: 200 μm.

Figure 5. Immunofluorescence (IF) co-staining demonstrating the colocalization of human CD98hc protein and the endothelial marker mCD31 in brain microvascular endothelial cells of huCD98HC(SLC3A2) mice (6-week-old females, homozygous, n=3).

3. 2% Evans Blue (EB) Blood-Brain Barrier Permeability Assay

2% Evans Blue (EB) was injected via the tail vein at a dose of 40 μL/10 g. Thirty minutes after injection, circulating EB was cleared by saline perfusion. Brain tissue observation showed that, compared with wild-type (WT) mice, huCD98HC(SLC3A2) mice did not exhibit obvious signs of blood-brain barrier damage.

Figure 6. Assessment of blood-brain barrier integrity in huCD98HC(SLC3A2) mice (6 weeks old, female, homozygous, n=4).

4. Analysis of Immune Cell Subsets

Flow cytometry was used to examine the proportions of T cells, B cells, NK cells, dendritic cells (DCs), monocytes, and macrophages within the CD45+ cell population in the bone marrow, blood, and spleen of huCD98HC(SLC3A2) mice and wild-type (WT) mice. Data are presented as mean ± SEM. Multiple unpaired t-tests were used to compare the proportions of each subset between huCD98HC(SLC3A2) and WT mice in each tissue. No statistically significant differences were observed in any comparison (p > 0.05).

Figure 7. Flow cytometric analysis of immune cell subset proportions (% of CD45+ cells) in the bone marrow, blood, and spleen of huCD98HC(SLC3A2) and wild-type (WT) mice (6-7 weeks old, female, homozygous, n=3).

5. Complete Blood Count (CBC)

Table 1. Hematological parameters of huCD98HC(SLC3A2) and wild-type (WT) mice (6 weeks old, female, homozygous, n=3). Values are expressed as mean ± SEM.

huCD98HC(SLC3A2) Mouse

基本情報

検証 Data

関連リソース

遺伝子名

遺伝子別名

NCBI ID

染色体

MGI ID

さらに

データシート

系統詳細

参考文献

系統作製戦略

適用分野

1. Gene Expression

2. Protein Expression

3. 2% Evans Blue (EB) Blood-Brain Barrier Permeability Assay

4. Analysis of Immune Cell Subsets

5. Complete Blood Count (CBC)

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