The CNR1 gene (Cannabinoid Receptor 1) encodes the CB1 receptor, a highly conserved G protein-coupled receptor (GPCR) that serves as the primary molecular target for endocannabinoids like anandamide and exogenous cannabinoids like THC. It is most abundantly expressed in the central nervous system, particularly in the cerebral cortex, hippocampus, basal ganglia, and cerebellum, but is also present in peripheral tissues such as the liver, adipose tissue, and gastrointestinal tract ^[1]. Functionally, CB1 receptors primarily reside on presynaptic terminals where they regulate neurotransmitter release—typically inhibiting the release of GABA or glutamate—to modulate pain, appetite, memory, and emotional processing ^[2]. Dysregulation of CNR1 expression or CB1 signaling is strongly associated with a variety of diseases, including obesity, metabolic syndrome, chronic pain, and neuropsychiatric disorders, such as anxiety, depression, and schizophrenia ^[3-4]. The huCNR1 mouse is a humanized model constructed by using gene-editing technology to replace the sequence from the ATG start codon to the TGA stop codon in the endogenous mouse Cnr1 gene with the sequence from the ATG start codon to the TGA stop codon in the human CNR1 gene. This model can be used for research related to obesity, metabolic syndrome, chronic pain, and neuropsychiatric diseases, such as anxiety, depression, and schizophrenia, as well as for the development of CNR1-targeted drugs.

Cannabinoid receptor 1 (CNR1) is a member of the G protein-coupled receptor (GPCR) superfamily, predominantly expressed in the central nervous system regions, including the cerebral cortex, hippocampus, basal ganglia, and cerebellum ^[1]. CNR1 binds to endocannabinoids and mediates retrograde trans-synaptic signaling, modulating the release of neurotransmitters such as GABA and glutamate, thereby regulating diverse physiological processes including appetite, energy metabolism, mood, cognition, and addiction ^[2]. Studies have shown that CNR1 dysfunction is closely associated with obesity, type 2 diabetes (T2D), schizophrenia, and substance dependence, establishing CNR1 as an important drug target for metabolic and neuropsychiatric diseases ^[3]. The huCNR1(2) mouse is a humanized model generated via gene editing. The sequences from the start codon to the 3'UTR of the endogenous mouse Cnr1 gene were replaced with the sequences from the start codon to the 3'UTR of the human CNR1 gene. This model is suitable for studying the mechanisms of metabolic and neuropsychiatric disorders, as well as for the screening, development, and preclinical in vivo evaluation of CNR1-targeted candidate drugs.

The Ifnar1 gene encodes the interferon-alpha/beta receptor 1 subunit, a critical mediator of the body's antiviral and immune responses. This gene is predominantly expressed in immune cells, including lymphocytes and dendritic cells, and is also present in various tissues such as the liver, brain, and skin. The protein product of Ifnar1 forms a receptor complex with Ifnar2, which is essential for the binding of interferons alpha and beta. This ligand-receptor interaction initiates a cascade of signaling pathways, culminating in the activation of genes responsible for antiviral protein production, cell growth inhibition, and immune cell recruitment. The Ifnar1 gene plays a pivotal role in host defense, regulating a broad spectrum of processes including cellular growth, survival, differentiation, pathogen resistance, and antiviral immunity. Mutations or dysregulation of Ifnar1 can result in severe pathologies, such as systemic lupus erythematosus, characterized by excessive immune activation and tissue damage, or certain cancers, where compromised interferon signaling undermines anti-tumor immunity. This strain represents a model of Ifnar1 knockout (KO), constructed by the deletion of exon 2 (E2) of the mouse Ifnar1 gene. This modification leads to a deficiency in the function of type I IFN receptors, resulting in a diminished immune response, heightened susceptibility to viral infections, and a decreased immune response to immunostimulatory DNA. Homozygous Ifnar1 KO mice are viable and fertile.

C1qc is located on chromosome 4 of mice. Nuclease Technology was used to design sgRNA; C1qc knockout mice were obtained by applying high-throughput electroporation of fertilized eggs. After sexual maturity, sperm were collected for cryopreservation.

Aqp1 is located on chromosome 6 of mice. SgRNA and ssDNA will be designed using Nuclease Technology; Aqp1 conditional knockout mice will be obtained by high-throughput electroporation of fertilized eggs. After sexual maturity, sperm will be collected for cryopreservation.