Axonal Regeneration and Neuronal Function Are Preserved in Motor Neurons Lacking ß-Actin In Vivo

Abstract

The proper localization of ß-actin mRNA and protein is essential for growth cone guidance and axon elongation in cultured neurons. In addition, decreased levels of ß-actin mRNA and protein have been identified in the growth cones of motor neurons cultured from a mouse model of Spinal Muscular Atrophy (SMA), suggesting that ß-actin loss-of-function at growth cones or pre-synaptic nerve terminals could contribute to the pathogenesis of this disease. However, the role of ß-actin in motor neurons in vivo and its potential relevance to disease has yet to be examined. We therefore generated motor neuron specific ß-actin knock-out mice (Actb-MNsKO) to investigate the function of ß-actin in motor neurons in vivo. Surprisingly, ß-actin was not required for motor neuron viability or neuromuscular junction maintenance. Skeletal muscle from Actb-MNsKO mice showed no histological indication of denervation and did not significantly differ from controls in several measurements of physiologic function. Finally, motor axon regeneration was unimpaired in Actb-MNsKO mice, suggesting that ß-actin is not required for motor neuron function or regeneration in vivo.

Axonal transport of neural membrane protein 35 mRNA increases axon growth

“…It seems likely that protein products of other axonal mRNAs also contribute to regeneration of axons. Consistent with this, mice lacking the b-actin gene apparently showed normal development and regeneration of motor axons (Cheever et al, 2011). This could indicate that b-actin is not needed for regeneration, or that other locally synthesized proteins can compensate for the loss of b-actin.…”

Restricted Morphological and Behavioral Abnormalities following Ablation of β-Actin in the Brain

“…Embryos were genotyped from tail snip lysates following protocols described previously [17]. 80,000 neurons were plated in 35 mm dishes containing acid washed coverslips coated with Poly-D-Lysine (100 µg/ml) and laminin (4 µg/ml).…”

Targeted Depletion of TDP-43 Expression in the Spinal Cord Motor Neurons Leads to the Development of Amyotrophic Lateral Sclerosis-like Phenotypes in Mice

“…Also, HB9:Cre mice express the cre gene specifically in the spinal cord motor neurons and have been used previously to manipulate gene expression in the motor neurons (33). The motor neuron specificity of the HB9-driven Cre expression have also been verified by crossing the HB9:Cre mouse line to a ROSA26:LacZ reporter mice in several studies (33)(34)(35)(36)(37)(38). Examination of the GFP signals in HB9:GFP transgenic mice have indicated that expression of HB9 is restricted in the motor neurons, but not in the sensory neurons (39).…”