Figure 1

Clec4a3 is cis -regulated after nerve root injury and the Aplec complex confers neuroprotection. The inbred DA and PVG rat strains display considerable, genetically determined, differences in spinal cord motor neuron survival following VRA. Global expressional profiling of lesioned spinal cord ventral horn tissue from an F2 (DAxPVG) intercross reveals several strong eQTLs. One of the strongest eQTLs among more than 27,000 transcripts is Clec4a3, a C-type lectin with hitherto unknown function in the CNS. Clec4a3 was cis-regulated from chromosome 4 (A) from marker D4Got130 (B). All F2 animals were genotyped over the whole genome and the PVG genotype in marker D4Got130 was found to lead to higher expression of Clec4a3 (C), with highest expression in PVG homozygotes; the heterozygotes displayed an intermediate phenotype. The Aplec congenic strain, which has a small fragment from PVG onto DA background containing six characterized C-type lectin genes including Clec4a3, displays significantly improved motor neuron survival compared to DA at 21 days after VRA (D). A representative section from the L4 segment shows motor neurons in the ventral horn on the contralateral (CL) and ipsilateral (IL) sides of the cord (axotomized cells are indicated by arrows) in one Aplec (E and G) and one DA (F and H) rat. In A the x-axis marks each chromosome and in B it is the genetic distance on chromosome 4 measured in centimorgans (cM); the y-axis shows the logarithm of odds (LOD)-score, where LOD > 3.1 corresponds to a genome wide P < 0.001, and the current LOD-score of around 20 to P = 0. The scale bar in the micrographs corresponds to 80 μm. Aplec: antigen-presenting lectin-like receptor gene complex; CL: contralateral; CNS: central nervous system; eQTL: expression quantitative trait loci; IL: ipsilateral; LOD: logarithm of odds; VRA: ventral root avulsion.