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CRISPR Rabbits for Cystic Fibrosis Research 
Cystic fibrosis (CF) is a fatal autosomal recessive disease caused by mutations in the gene encoding the cystic fibrosis transmembrane conductance regulator (CFTR). Animal models of CF have undoubtedly contributed to the understanding of disease pathogenesis and the development of therapeutic agents, but the existing models (mouse, rat, ferret, sheep, and pig) have limitations. From a scientific point of view, they can neither reproduce the main lung phenotypes observed in CF patients nor address the key pathophysiological questions. In terms of molecular pathogenesis studies and treatment, the amino acid sequence of rabbit CFTR is approximately 92% identical to human CFTR. In addition, rabbit lungs do not have submucosal glands and have a structure similar to the human distal airways, allowing the study of the distal airway region in the pathogenesis of CF lung disease. Therefore, rabbits are well suited for generating animal models of CF.
Fig. 1 Altered gastrointestinal function in CF rabbits. (Xu J, et al., 2021)
Solution
Creative Biogene's team has built a robust platform to generate knockout and knock-in rabbit models. We used a proven gene editing platform via CRISPR/Cas9 in New Zealand White rabbits to produce CF founder rabbits. Due to the inherent nature of CRISPR/Cas9-mediated gene targeting, in which specific mutation types are often unpredictable, founder animals carry different mutant alleles. Therefore, we bred founder animals with wild-type rabbits to verify germline transmission and established multiple CF rabbit models with insertion or deletion types.
Related Analytical Services
- Histopathological analysis of CF rabbit intestine for the detection of intestinal disorders (e.g., meconium intestinal obstruction) in CF rabbits.
- Liver pathology analysis of CF rabbits, including lipid metabolism assays, involving plasma lipase, triglycerides, and cholesterol.
- Histological analysis of pancreatic tissue in CF rabbits for assessment of foci of exocrine gland dilation, fibrosis, and inflammatory cell infiltration.
- Functional and structural analysis of the CF rabbit airway: detection of CFTR mRNA transcripts, protein expression, and function in the upper and lower respiratory tract.
What Choose Us?
Our CRISPR/Cas9-mediated rabbit CFTR gene modification provides a useful model for the study of CF pathogenesis and treatment. Our rabbit model of CF exhibits robust functional readouts of CFTR, including
- Classical NPD measurements and spontaneous development of upper airway pathology
- Abnormal GI bioelectric properties associated with weight loss and mortality
- CFTR proteins responsive to human CFTR modulators, including VX770
- Lower airway fine bronchial CFTR expression and abnormal bioelectric properties
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CRISPR/Cas9 PlatformCB is dedicated to providing customized gene editing rabbit models to facilitate CF disease research and drug development. Our scientists have extensive experience in the experimental operation and data processing of CRISPR systems. We guarantee a high-quality service to meet your project needs. If you are interested in our services, please feel free to contact us.
Reference:
- Xu J, et al. Phenotypes of CF rabbits generated by CRISPR/Cas9-mediated disruption of the CFTR gene. JCI Insight. 2021, 6(1):e139813.