The IL6RA (IL6R, also known as CD126) gene encodes a subunit of the interleukin-6 (IL-6) receptor complex. The IL-6 receptor is a protein complex composed of the IL6RA protein and the interleukin-6 signal transducer (IL6ST/GP130/IL6-beta). This receptor subunit is shared by many other cytokines. The expression of IL-6R is primarily restricted to hepatocytes, leukocytes, and megakaryocytes. Upon binding to its receptor IL-6Rα, IL-6 interacts with two GP130 molecules to form a hexameric complex in a 2:2:2 configuration. Once the IL-6 receptor complex is activated, multiple downstream events allow IL-6 to mediate its diverse effects. These include the pathways of the GTPase Ras and its effector Raf, the mitogen-activated protein kinase cascade that controls cellular proliferation and differentiation, and the pathways involving tyrosine kinases of the Jak family and transcription factors of the STAT family ^[1]. IL-6 receptor defects can lead to immunodeficiency and atopy. Patients with loss-of-function variants in IL-6R present with an autosomal recessive disorder characterized by recurrent Haemophilus chest infections, staphylococcal skin abscesses, atopic dermatitis, elevated IgE levels, eosinophilia, and absent acute phase responses ^[2]. Research has shown that the IL-6 pathway is crucial for maintaining homeostasis and is involved in the dysregulation seen in many diseases. Antibody drugs targeting the IL-6/IL-6 receptor signaling pathway have become innovative therapies for autoimmune diseases and cancers ^[3]. The hIL6RA mouse is an Il6ra gene humanized model, in which the coding sequence (CDS) of the human IL6R gene is inserted into the endogenous Il6ra gene sequence of mice. This model can be used in researching autoimmune diseases, inflammation-related diseases, cancer, and infectious diseases. It is also useful for the development, screening, and evaluation of IL6RA-targeted drugs.

Pcm1 is located on chromosome 8 of mice. Nuclease Technology will be used to design sgRNA; Pcm1 knockout mice will be obtained by applying high-throughput electroporation of fertilized eggs. After sexual maturity, sperm were collected for cryopreservation.

Vmn1r229 is located on chromosome 17 of mice. SgRNA and ssDNA will be designed using Nuclease Technology; Vmn1r229 conditional knockout mice will be obtained by high-throughput electroporation of fertilized eggs. After sexual maturity, sperm will be collected for cryopreservation.