This significance is born out of the fact that the first evidence of association between ALS pathology and VEGF came when Oosthuyse et al. created homozygous VEGF (VEGFδ/δ) knock-in mice by introducing homozygous mutation of hypoxia response element (HRE) in the VEGF gene promoter to study angiogenic property of VEGF. They observed that almost 60% of mice did not survive before or around birth due to vasculature aberrations in lungs. The gene discussed is VEGFA; the disease is amyotrophic lateral sclerosis.