Tbcd-flox Mouse

TBCD, short for tubulin-folding co-factor D, is one of five tubulin-specific chaperones. It is crucial for the proper folding and assembly of tubulin subunits, which are essential for microtubule formation. Microtubules play key roles in various cellular processes such as cell division, intracellular transport, and maintaining cell structure [1,2,3,4,5,6,7,8].

Mutations in TBCD have been associated with a range of neurodegenerative and neurodevelopmental disorders. In humans, biallelic TBCD mutations lead to early-onset progressive neurodegenerative encephalopathy, characterized by features like early-onset (before 1 year of age) progressive diffuse brain atrophy, postnatal microcephaly, growth retardation, muscle weakness, and respiratory failure [4]. Other phenotypes include distal motorneuronopathy, mild mental retardation, and corpus callosum hypoplasia [3]. In in vitro cell experiments, most mutant TBCD proteins showed impaired binding to ARL2, TBCE, and β-tubulin, and in vivo experiments using Drosophila melanogaster olfactory projection neurons indicated loss of function due to TBCD mutations [4].

In conclusion, TBCD is vital for microtubule assembly in all cells, with its disruption leading to severe neurodegenerative and neurodevelopmental conditions. Studies on TBCD-related mutations in humans provide insights into the pathomechanisms of these disorders, highlighting the importance of TBCD in maintaining normal neuronal function and development [1,3,4,5,6,7,8].