Cluster of Differentiation 20 (CD20), encoded by the membrane spanning 4-domains A1 (MS4A1) gene, is a transmembrane phosphoprotein primarily expressed on the surface of B cells. Throughout B cell development, from pro-B cell to memory B cell stages, CD20 is expressed, but is absent in early pro-B cells and plasma cells ^[1]. Belonging to the MS4A family of four-transmembrane domain proteins, CD20 modulates B cell activation and proliferation by regulating calcium signaling, potentially acting as a calcium channel or co-receptor to amplify B cell receptor (BCR) responses ^[1]. As a key biomarker for B cell malignancies, including B-cell lymphomas, chronic lymphocytic leukemia, and hairy cell leukemia, CD20 serves as a target for therapeutic monoclonal antibodies such as rituximab and obinutuzumab, enabling the depletion of pathogenic B cells in autoimmune diseases and cancers ^[2-3]. Disruption of MS4A1 is associated with immunodeficiency common variable type 5 (CVID5), characterized by hypogammaglobulinemia, recurrent infections, and impaired antibody production due to aberrant B cell differentiation ^[4]. Recent studies have also revealed a role for CD20 in olfactory sensory neurons, where it mediates innate predator-avoidance behaviors in mice by detecting predator-derived odorants ^[5]. This dual functionality underscores the protein's significance in both immune regulation and sensory biology. The B6-hCD20 mouse is a humanized model generated using gene editing technology to replace the entire base sequence of the mouse Ms4a1 gene in situ with the corresponding sequence from the human MS4A1 gene. Homozygous B6-hCD20 mice are viable and fertile. This model can be used for studying the pathological mechanisms and therapeutic approaches of autoimmune diseases and cancers, and for the development of CD20-targeted drugs.

The inhibin βC subunit (INHBC) is a member of the transforming growth factor-β (TGF-β) superfamily. Its encoded precursor protein undergoes hydrolytic processing to form homodimers or heterodimeric activin complexes with βA/βB subunits, which are involved in inhibiting the activin A signaling pathway and regulating multiple physiological processes. INHBC is abundantly expressed in the liver and also participates in the regulation of hormone secretion in the reproductive system ^[1-2]. Studies have confirmed that circulating INHBC is associated with reduced subcutaneous fat, dyslipidemia, and increased risks of coronary artery disease (CAD) and non-alcoholic fatty liver disease (NAFLD). Meanwhile, obesity, hypertriglyceridemia, type 2 diabetes mellitus, and other conditions positively regulate plasma INHBC levels. Recombinant INHBC (Act-C) can inhibit lipolysis in adipocytes by activating the ALK7-SMAD2/3 signaling pathway, further clarifying its role in metabolic regulation ^[3]. The inhibin βE subunit (INHBE) is also a member of the TGF-β superfamily, with highly specific expression in hepatocytes. The precursor protein of INHBE generates the inhibin β subunit after proteolytic processing. This protein is associated with various cellular processes, including cell proliferation, apoptosis, immune response, and hormone secretion. During the development of obesity and diabetes, the expression of INHBE protein inhibits the proliferation and growth of relevant cells in the pancreas and liver. Research has found a positive correlation between INHBE expression in the liver and insulin resistance and body mass index (BMI), suggesting that INHBE may be a liver factor in altering systemic metabolic status under conditions of obesity-related insulin resistance ^[4]. The studies conducted by Alnylam Pharmaceuticals and the Regeneron Genetics Center (RGC) revealed the close relationship between INHBE and fat regulation. The research demonstrated that rare loss-of-function variants in INHBE may protect the liver from the impact of inflammation, abnormal blood lipids, and type 2 diabetes by promoting healthy fat storage. Patients carrying such mutations exhibit more normal fat distribution, significantly reduced abdominal fat, improved metabolic conditions, and a decreased risk of cardiovascular diseases and type 2 diabetes ^[5-7]. These findings suggest that INHBE is a liver-specific negative regulator of fat storage. Inhibiting the expression of INHBE genes and proteins may be a promising strategy for treating metabolic disorders associated with improper fat distribution and storage. The huINHBC/huINHBE mouse is a dual-gene humanized model established via gene editing technology. In this model, the sequences from upstream of the mouse Inhbc exon 1 to the mouse Inhbe 3'UTR were replaced with the sequences from upstream of the human INHBC exon 1 to 3'UTR of the human INHBE. This model can be utilized for investigating the mechanisms and therapeutic approaches of fat distribution and storage, dyslipidemia, CAD, NAFLD, as well as for the development of INHBC/INHBE-targeted drugs.

Abca1 is located on chromosome 4 of mice. SgRNA and ssDNA were designed using Nuclease Technology; Abca1 conditional knockout mice were obtained by high-throughput electroporation of fertilized eggs. After sexual maturity, sperm were collected for cryopreservation.

4931406C07Rik is located on chromosome 9 of mice. Nuclease Technology was used to design sgRNA; 4931406C07Rik knockout mice were obtained by applying high-throughput electroporation of fertilized eggs. After sexual maturity, sperm were collected for cryopreservation.

4931406C07Rik is located on chromosome 9 of mice. Nuclease Technology was used to design sgRNA; 4931406C07Rik knockout mice were obtained by applying high-throughput electroporation of fertilized eggs. After sexual maturity, sperm were collected for cryopreservation.

4931422A03Rik is located on chromosome 2 of mice. Nuclease Technology will be used to design sgRNA; 4931422A03Rik knockout mice will be obtained by applying high-throughput electroporation of fertilized eggs. After sexual maturity, sperm were collected for cryopreservation.

4931414P19Rik is located on chromosome 14 of mice. Nuclease Technology will be used to design sgRNA; 4931414P19Rik knockout mice will be obtained by applying high-throughput electroporation of fertilized eggs. After sexual maturity, sperm were collected for cryopreservation.

4931429L15Rik is located on chromosome 9 of mice. Nuclease Technology will be used to design sgRNA; 4931429L15Rik knockout mice will be obtained by applying high-throughput electroporation of fertilized eggs. After sexual maturity, sperm were collected for cryopreservation.