Generation and characterization of pathogenic Mab21l2(R51C) mouse model

Area of Science:

• Developmental Biology
• Genetics
• Medical Research

Background:

• MAB21L2 mutations are linked to human developmental disorders, including eye malformations, skeletal dysplasia, and intellectual disability.
• The specific MAB21L2(R51C) mutation has been identified in patients but requires further functional investigation.

Purpose of the Study:

• To create and characterize a mouse model for the MAB21L2(R51C) mutation to understand its role in human development.
• To systematically evaluate the pathological features associated with this specific MAB21L2 mutation.

Main Methods:

• Introduction of the R51C mutation into the mouse genome using CRISPR/Cas9 gene editing.
• Phenotypic analysis of mutant mice, including micro-computed tomography (micro-CT) and histological examination.
• Comparative analysis between Mab21l2 ^R51C/+ mice and wild-type littermates.

Main Results:

• Mab21l2 ^R51C/+ mice display an eyeless phenotype and significant skeletal abnormalities, including joint fusions (humerus-radius, femur-tibia) and shortened limbs.
• Micro-CT revealed the absence of eyeballs and the presence of abnormal tissues beneath the brain in mutant mice.
• Histological analysis confirmed interrupted early eye development and absent deltoid tuberosities in the humeri of mutant mice.

Conclusions:

• The Mab21l2 ^R51C/+ mouse model successfully recapitulates the key pathological features of MAB21L2-related human developmental disorders.
• This model provides a valuable platform for investigating the molecular mechanisms underlying optic differentiation and skeletogenesis affected by MAB21L2 mutations.
• Further studies using this model will elucidate the specific pathogenic mechanisms of the MAB21L2(R51C) mutation in human development.