The CD22 gene encodes a 140 kDa type I transmembrane glycoprotein that serves as a critical member of the SIGLEC (sialic acid-binding immunoglobulin-like lectin) family. Gene expression is highly restricted to B-lymphocytes, with strong surface expression on mature B cells and high RNA levels in lymphoid tissues such as lymph nodes and spleen ^[1]. The encoded protein functions as a potent inhibitory co-receptor of the B-cell receptor (BCR); upon ligand binding, its cytoplasmic immunoreceptor tyrosine-based inhibitory motifs (ITIMs) are phosphorylated, recruiting phosphatases like SHP-1 to attenuate B-cell activation and maintain peripheral tolerance ^[2]. Beyond its regulatory role, CD22 facilitates cell-cell adhesion by recognizing α2,6-linked sialic acids. Due to its restricted expression pattern, CD22 is a major diagnostic marker and therapeutic target in various B-cell malignancies, including hairy cell leukemia, B-cell non-Hodgkin lymphoma, and acute lymphoblastic leukemia (ALL), and it has also been implicated in the pathogenesis of autoimmune disorders such as systemic lupus erythematosus (SLE) ^[3]. The huCD22 mouse model was generated by replacing the murine Cd22 sequence from aa.22 through exon 9 with the homologous human CD22 region, all while retaining the mouse signal peptide to facilitate appropriate protein expression. This model is applicable to the study of various autoimmune diseases, including systemic lupus erythematosus (SLE), as well as cancers such as hairy cell leukemia, B-cell non-Hodgkin lymphoma, and acute lymphoblastic leukemia (ALL), and to the development of CD22-targeted therapeutics.

The OPA1 gene (Mitochondrial Dynamin Like GTPase) is a nuclear-encoded gene that is ubiquitously expressed in human tissues, with particularly high levels in the retina (specifically retinal ganglion cells), brain, heart, and skeletal muscle. It encodes a large dynamin-related GTPase protein that exists as eight distinct isoforms due to alternative splicing; these are further processed into membrane-anchored long forms (L-OPA1) and soluble short forms (S-OPA1) ^[1]. This protein localizes to the inner mitochondrial membrane and the intermembrane space, where it plays a critical functional role in mediating mitochondrial fusion, maintaining the structural integrity of cristae, and regulating cytochrome c sequestration to prevent apoptosis ^[2]. Mutations in OPA1 are primarily associated with Autosomal Dominant Optic Atrophy (ADOA), the most common form of hereditary optic neuropathy characterized by the progressive degeneration of retinal ganglion cells and blindness, as well as more severe "ADOA-plus" syndromes and Behr syndrome, which include multisystemic symptoms such as sensorineural deafness, ataxia, peripheral neuropathy, and chronic progressive external ophthalmoplegia (CPEO) ^[3-4]. The c.2708_2711del mutation is one of the most frequently reported causes of Autosomal Dominant Optic Atrophy (ADOA) worldwide. The huOPA1-del(c.2708-2711) mouse is a humanized model with a c.2708_2711del TTAG mutation. In this model, the sequence from upstream of exon 1 to downstream of 3’UTR of the mouse Opa1 was replaced with the sequence from upstream of exon 1 to downstream of 3’UTR of the human OPA1. Specifically, the c.2708_2711del TTAG mutation is introduced into exon 27 of the human OPA1 gene. This model is suitable for the study of Autosomal Dominant Optic Atrophy (ADOA), as well as for the development of OPA1-targeted therapies.

Adora1 is located on chromosome 1 of mice. Nuclease Technology was used to design sgRNA; Adora1 knockout mice were obtained by applying high-throughput electroporation of fertilized eggs. After sexual maturity, sperm were collected for cryopreservation.

Zfp933 is located on chromosome 4 of mice. Nuclease Technology will be used to design sgRNA; Zfp933 knockout mice will be obtained by applying high-throughput electroporation of fertilized eggs. After sexual maturity, sperm were collected for cryopreservation.

Zfp933 is located on chromosome 4 of mice. SgRNA and ssDNA will be designed using Nuclease Technology; Zfp933 conditional knockout mice will be obtained by high-throughput electroporation of fertilized eggs. After sexual maturity, sperm will be collected for cryopreservation.

4933411K16Rik is located on chromosome 19 of mice. Nuclease Technology will be used to design sgRNA; 4933411K16Rik knockout mice will be obtained by applying high-throughput electroporation of fertilized eggs. After sexual maturity, sperm were collected for cryopreservation.

4933428M09Rik is located on chromosome X of mice. Nuclease Technology will be used to design sgRNA; 4933428M09Rik knockout mice will be obtained by applying high-throughput electroporation of fertilized eggs. After sexual maturity, sperm were collected for cryopreservation.

4933412E24Rik is located on chromosome 15 of mice. Nuclease Technology will be used to design sgRNA; 4933412E24Rik knockout mice will be obtained by applying high-throughput electroporation of fertilized eggs. After sexual maturity, sperm were collected for cryopreservation.

4933403O08Rik is located on chromosome X of mice. Nuclease Technology will be used to design sgRNA; 4933403O08Rik knockout mice will be obtained by applying high-throughput electroporation of fertilized eggs. After sexual maturity, sperm were collected for cryopreservation.

4933402D24Rik is located on chromosome 1 of mice. Nuclease Technology will be used to design sgRNA; 4933402D24Rik knockout mice will be obtained by applying high-throughput electroporation of fertilized eggs. After sexual maturity, sperm were collected for cryopreservation.