Generation of mouse conditional and null alleles of the type III sodium-dependent phosphate cotransporter PiT-1.
Accelerated vascular calcification occurs in several human diseases including diabetes and chronic kidney disease (CKD). In patients with CKD, vascular calcification is highly correlated with elevated serum phosphate levels. In vitro, elevated concentrations of phosphate induced vascular smooth muscle cell matrix mineralization, and the inorganic phosphate transporter-1 (PiT-1), was shown to be required. To determine the in vivo role of PiT-1, mouse conditional and null alleles were generated. Here we show that the conditional allele, PiT-1(flox), which has loxP sites flanking exons 3 and 4, is homozygous viable. Cre-mediated recombination resulted in a null allele that is homozygous lethal. Examination of early embryonic development revealed that the PiT-1(Deltae3,4/Deltae3,4) embryos displayed anemia, a defect in yolk sac vasculature, and arrested growth. Thus, conditional and null PiT-1 mouse alleles have been successfully generated and PiT-1 has a necessary, nonredundant role in embryonic development.
Festing
Maria H
MH
Department of Bioengineering, University of Washington, Seattle, Washington, USA.
Speer
Mei Y
MY
Yang
Hsueh-Ying
HY
Giachelli
Cecilia M
CM
D000483:Alleles; D000818:Animals; D004622:Embryo, Mammalian / Q000196:embryology / Q000378:metabolism; D005260:Female; D018507:Gene Expression Regulation, Developmental; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008808:Mice, Inbred CBA; D008811:Mice, Inbred DBA; D008815:Mice, Inbred Strains; D018345:Mice, Knockout; D008822:Mice, Transgenic; D009154:Mutation; D011247:Pregnancy; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013997:Time Factors; D050817:Transcription Factor Pit-1 / Q000235:genetics* / Q000502:physiology
D050817:Transcription Factor Pit-1; C494185:Pou1f1 protein, mouse