Identification of sensory dysfunction and nervous structure changes in Fam134b knockout mice

Area of Science:

• Neuroscience
• Genetics
• Molecular Biology

Background:

• Hereditary sensory and autonomic neuropathy type IIB is linked to mutations in the human FAM134B gene.
• Understanding FAM134B's function is crucial for developing treatments for this neuropathy.

Purpose of the Study:

• To create a Fam134b knockout mouse model.
• To investigate the phenotypic consequences of Fam134b gene knockout.
• To determine if the mouse model replicates human neuropathy manifestations.

Main Methods:

• CRISPR/Cas9 technology was employed to generate Fam134b knockout mice.
• Sanger sequencing and Western blot confirmed gene knockout and protein expression loss.
• Sensory function was assessed via hot plate and paw withdrawal tests; structural analysis used microscopy.

Main Results:

• Fam134b knockout mice displayed heat pain insensitivity and mechanical hyperalgesia.
• Observed demyelination in the sciatic nerve and turgid Golgi bodies in dorsal root ganglion neurons.
• Some homozygotes exhibited limb damage, indicating peripheral neuropathy.

Conclusions:

• Fam134b knockout mice present common peripheral neuropathy phenotypes.
• This novel animal model offers a reliable platform for studying peripheral neuropathy and its complications.
• The model facilitates research into therapeutic strategies for FAM134B-associated neuropathies.