Acan (aggrecan) encodes aggrecan, the principal chondroitin sulfate proteoglycan of the cartilage extracellular matrix. Its core protein binds hyaluronan and link protein through the N-terminal G1 domain to form proteoglycan aggregates, and the chondroitin sulfate glycosaminoglycan chains give the matrix a high negative charge density, contributing to the compressive resistance and structural integrity of cartilage ^[1]. Acan has been reported to be expressed in chondrocytes of the growth plate and articular cartilage ^[1]. In the central nervous system, Acan is expressed by neurons and is the major chondroitin sulfate proteoglycan component of perineuronal nets (PNNs); Acan mRNA has been detected in the cerebral cortex, hippocampus, deep cerebellar nuclei, brain stem nuclei and spinal cord ^[2]. Acan-P2A-iCre mice were generated by gene editing, in which the stop codon of the endogenous mouse Acan gene was replaced with the "P2A-iCre" cassette. When Acan-P2A-iCre mice are crossed with mice carrying loxP sites, the offspring are expected to undergo iCre recombinase-mediated recombination between loxP sites in Acan-positive cells. The model can be used for studies on Acan-positive chondrocytes and neurons.

Adamts13 (a disintegrin and metallopeptidase with thrombospondin type 1 motif 13) encodes ADAMTS13, also known as von Willebrand factor-cleaving protease (VWFCP). ADAMTS13 is a zinc-dependent metalloprotease that cleaves ultra-large von Willebrand factor (VWF) multimers and thereby limits VWF-mediated platelet adhesion and microthrombus formation ^[1]. Plasma ADAMTS13 is reported to be synthesized and secreted mainly by hepatic stellate cells in the liver, with small amounts also produced by vascular endothelial cells, glomerular podocytes and glial cells in the central nervous system ^[1]. Adamts13-iCre-P2A-EGFP mice were generated by gene editing, in which the "Kozak-iCre-P2A-EGFP-T2A" cassette was inserted upstream of the ATG start codon of the endogenous mouse Adamts13 gene. When Adamts13-iCre-P2A-EGFP mice are crossed with mice carrying loxP sites, the offspring are expected to undergo iCre recombinase-mediated recombination between loxP sites in Adamts13-positive cells.

Adam11 (a disintegrin and metallopeptidase domain 11) encodes ADAM11, a member of the ADAM family and a type I transmembrane protein. Because key residues of the catalytic motif are absent, ADAM11 is generally considered to lack metalloproteinase activity; in the central nervous system it has been implicated in neuronal adhesion and in the localization of presynaptic proteins ^[1,2]. Adam11 has been reported to be expressed in neurons throughout the central nervous system, with relatively high levels in the cerebellar cortex ^[1]; at the protein level, ADAM11 is enriched at cerebellar basket cell axon terminals (pinceau) and is weakly expressed in Purkinje cells, with expression also detected in the cerebral cortex, brain stem nuclei and spinal cord ^[2]. Expression has additionally been detected in the retina, peripheral nervous system ganglia, liver and testis, and at lower levels in the kidney ^[1]. Adam11-3xV5 tag-P2A-iCreERT2-T2A-3xNLS-3xHA tag mice were generated by gene editing, in which the stop codon of the endogenous mouse Adam11 gene was replaced with the "3xV5 tag-P2A-iCreERT2-T2A-3xNLS-3xHA tag" cassette. In the absence of tamoxifen treatment, the iCreERT2 recombinase is mainly localized in the cytoplasm; after tamoxifen treatment, the iCreERT2 recombinase enters the nucleus and exerts its recombination function. When Adam11-3xV5 tag-P2A-iCreERT2-T2A-3xNLS-3xHA tag mice are crossed with mice carrying loxP sites, the offspring are expected to undergo Cre recombinase-mediated recombination between loxP sites in Adam11-positive cells after tamoxifen induction.

Adcyap1 (adenylate cyclase activating polypeptide 1; also known as PACAP) encodes the precursor of pituitary adenylate cyclase-activating polypeptide (PACAP), a member of the glucagon/secretin superfamily. The precursor is proteolytically processed into PACAP-27, PACAP-38 and PACAP-related peptide (PRP), and acts through PAC1 (Adcyap1r1), VPAC1 and VPAC2 receptors as a neurotransmitter, neuromodulator and hypophysiotropic hormone ^[1]. PACAP is reported to be expressed mainly in neuronal cell bodies in the central nervous system: a high-resolution map of the mouse brain showed Adcyap1-expressing neurons in multiple hypothalamic nuclei (paraventricular nucleus, ventromedial nucleus, mammillary bodies and others), hippocampal CA1–CA3 pyramidal cells and hilar mossy cells, layer 2/3 and layer 5 pyramidal neurons of the cerebral cortex, the amygdala (lateral and basal nuclei), and brainstem regions including the parabrachial nucleus and the nucleus of the solitary tract ^[2]. Adcyap1-P2A-iCre mice were generated by gene editing, in which the stop codon of the endogenous mouse Adcyap1 gene was replaced with the "P2A-iCre" cassette. When Adcyap1-P2A-iCre mice are crossed with mice carrying loxP sites, the offspring are expected to undergo iCre recombinase-mediated recombination between loxP sites in Adcyap1-positive cells. The model can be used for studies on Adcyap1-positive neuropeptidergic neurons.

P-glycoprotein (P-gp), also known as multidrug resistance protein 1 (MDR1), is an ATP-binding cassette transporter that acts as a biological barrier by expelling toxins and foreign substances from cells. P-gp is capable of transporting many structurally and functionally different compounds out of cells ^[1]. However, the mechanism of MDR1 also prevents the uptake of many cancer treatment drugs by cells, leading to multidrug resistance (MDR) ^[2]. In normal organisms, MDR1’s distribution in the blood-brain barrier and blood-placenta barrier prevents exogenous drugs and toxins from entering the central nervous system and placenta of the organism, thereby protecting the organism and enabling it to perform normal physiological functions. In pathological conditions, however, the MDR1 in the blood-brain barrier prevents drugs from entering the central nervous system, and in tumor cells, leads to the development of MDR. The evolution of MDR remains one of the major obstacles to controlling or curing cancer ^[3-4]. In humans, the MDR1 protein is encoded by the ABCB1 gene. In mice, two closely located genes, Abcb1a and Abcb1b, encode the MDR1a and MDR1b subtypes of this protein. Mouse MDR1a and MDR1b have 80% homology with human MDR1. MDR1a and MDR1b have the same function as human MDR1 protein in resisting anticancer drugs. Although mouse MDR1a and MDR1b proteins are distributed in different tissues of the body, their overall distribution is consistent with that of human MDR1 protein ^[5-6]. In summary, the distribution and function of mouse MDR1a and MDR1b are consistent with those of human MDR1. This strain is an MDR1 knockout model, in which the human ABCB1 gene’s homologous genes, Abcb1a and Abcb1b, were knocked out in mice using gene editing technology. This model lacks the expression of MDR1 protein and can be used for research in areas such as blood-brain barrier permeability-related diseases and multidrug resistance of anti-tumor drugs.

Progressive Familial Intrahepatic Cholestasis Type 3 (PFIC3) is a rare, life-threatening autosomal recessive hereditary liver disease caused by mutations in the ABCB4 gene (also known as MDR3 in humans and MDR2 in rodents) ^[1-3]. The disease is characterized by early persistent cholestasis, leading to the accumulation of bile acids in the liver and subsequent hepatocellular damage. Clinical manifestations of PFIC3 include jaundice (yellowing of the skin and eyes), pruritus, fatigue, and growth failure. If untreated, it can progress to cirrhosis and liver failure in early childhood ^[4]. The ABCB4 gene encodes Multidrug Resistance Protein 3 (MDR3), a member of the ATP-binding cassette (ABC) transporter family, which is a liver-specific phosphatidylcholine (PC) transporter ^[5]. MDR3 is primarily expressed on the canalicular membrane of hepatocytes (the membrane that forms bile canaliculi). It is involved in the transport of phosphatidylcholine from the hepatocyte membrane to vesicles, which are then secreted into bile, forming PC-cholesterol vesicles and a small number of mixed bile salt micelles ^[6]. Mutations in ABCB4 lead to the loss or dysfunction of MDR3, reducing PC levels in bile, destabilizing micelles, and increasing bile salt concentrations, thereby causing cholestasis and hepatocellular injury ^[7]. Studies have shown that knocking out the Abcb4 gene in mice leads to a phenotype similar to human PFIC3, although the severity and progression of the disease vary across different mouse strains. In the commonly used C57BL/6 background, Abcb4-KO mice exhibit a relatively mild pathological phenotype due to lower bile salt toxicity, and a diet enriched in hydrophobic bile salts is typically required to induce a more human-like PFIC3 phenotype ^[8-10]. In contrast, Abcb4-KO mice in the FVB background naturally exhibit most of the biomarkers and pathological features of human PFIC3, including hepatomegaly, liver fibrosis, and early disease onset with more severe progression ^[10-11]. Cyagen has generated the Abcb4-KO(FVB) mouse model by knocking out the Abcb4 gene in FVB mice. This model lacks the Abcb4 gene and protein expression and exhibits liver enlargement, elevated liver function markers, and increased total bilirubin. Histopathological examination shows hepatocyte necrosis, inflammatory cell infiltration, connective tissue proliferation, bile duct proliferation, and liver fibrosis.

The Arl13b gene (ADP-ribosylation factor-like 13B) encodes ARL13B, a small GTPase belonging to the ADP-ribosylation factor-like (ARL) family. ARL13B localizes predominantly to the primary ciliary membrane and contributes to ciliogenesis, ciliary length regulation, and maintenance of axonemal structure. It also regulates the localization and dynamic distribution of Hedgehog signaling components, including Smoothened (SMO), within cilia, thereby contributing to Hedgehog signaling and dorsoventral patterning of the neural tube ^[1-2]. The Arl13b-3xEAAAK-EGFP mouse was generated using gene-editing technology to replace the stop codon of the mouse endogenous Arl13b gene with the 3xEAAAK-EGFP cassette. This model can be used for studies on Arl13b-positive cells and primary cilia.

The Arl13b gene (ADP-ribosylation factor-like 13B) encodes ARL13B, a small GTPase belonging to the ADP-ribosylation factor-like (ARL) family. ARL13B localizes predominantly to the primary ciliary membrane and contributes to ciliogenesis, ciliary length regulation, and maintenance of axonemal structure. It also regulates the localization and dynamic distribution of Hedgehog signaling components, including Smoothened (SMO), within cilia, thereby contributing to Hedgehog signaling and dorsoventral patterning of the neural tube ^[1-2]. The Arl13b-P2A-mCherry mouse was generated using gene-editing technology to replace the stop codon of the mouse endogenous Arl13b gene with the P2A-mCherry cassette. This model can be used for studies on Arl13b-positive cells and primary cilia.

The ADIPOQ gene-encoded adiponectin is a protein hormone produced exclusively by adipocytes (fat cells). It is transported through the bloodstream to muscle and liver cells. Adiponectin regulates various pathways related to fat storage and metabolism, including the modulation of blood glucose levels, fatty acid breakdown, brown adipocyte differentiation, and negative regulation of gluconeogenesis. By increasing insulin sensitivity and promoting fatty acid breakdown, adiponectin plays a crucial role in regulating glucose and fat metabolism. Additionally, it exhibits direct anti-diabetic, anti-atherosclerotic, and anti-inflammatory activities ^[1-2]. The mutation of the ADIPOQ gene is associated with adiponectin deficiency syndrome. Although the ADIPOQ gene is expressed predominantly (or almost exclusively) in adipose tissue, adiponectin, as a secreted hormone, circulates via the bloodstream and is widely distributed in various tissues and organs, including skeletal muscle, liver, intestine, male reproductive glands, and brain, where it exerts its physiological effects through specific receptors (such as AdipoR1 and AdipoR2) ^[3-4]. The Adipoq-P2A-iCre mice are constructed by inserting a codon-improved Cre recombinase (iCre) element into the endogenous Adipoq gene of mice. The expression pattern of iCre recombinase is similar to the endogenous gene. When this strain is crossed with mice containing loxP sites, sequence recombination mediated by the Cre recombinase between loxP sites can occur in the white adipose tissue (WAT) and brown adipose tissue (BAT) of its offspring.