A targeting vector was designed to remove exons 3-4 of the solute carrier family 20, member 1 (Slc20a1 or inorganic phosphate transporter-1 PiT-1) gene, in the epiblast, yolk sac mesoderm, and amnion, abolishing gene function. Mice that are heterozygous for this PiT-1Δe3,4 allele are viable, fertile, normal in size and do not display any gross physical or behavioral abnormalities, while homozygotes display an embryonic lethal phenotype. PiT-1, a ubiquitously expressed transmembrane type III sodium-dependent transporter, is associated with vascular calcification in many diseases, including diabetes, chronic kidney disease (CKD), and Werner Syndrome. The yolk sacs of homozygous embryos reveal a decrease in the superficial vasculature and appear severely anemic by E10.5. By E12.5, the embryos display significant growth retardation and anemia, leading to hypoxia, nutrient deprivation, growth arrest, and lethality. These homozygous PiT-1Δe3,4 embryos are completely resorbed by E14.5.
