Urea movement across plasma membranes is modulated by specialized transport
er proteins that are products of two genes, termed UT-A and UT-B. These pro
teins play key roles in the urinary concentrating mechanism and fluid homeo
stasis. We have isolated and characterized a 1.4-kb cDNA from testes encodi
ng a new isoform (UT-A5) belonging to the UT-A transporter family. For comp
arison, we also isolated a 2.0-kb cDNA from mouse kidney inner medulla enco
ding the mouse UT-A3 homologue. The UT-A5 cDNA has a putative open reading
frame encoding a 323- amino acid protein, making UT-A5 the smallest UT- A f
amily member in terms of molecular size. Its putative topology is of partic
ular interest, because it calls into question earlier models of UT-A transp
orter structure. Expression of UT-A5 cRNA in Xenopus oocytes mediates phlor
etin-inhibitable urea uptake and does not translocate water. The distributi
on of UT-A5 mRNA is restricted to the peritubular myoid cells forming the o
utermost layer of the seminiferous tubules within the testes and is not det
ected in kidney. UT-A5 mRNA levels are coordinated with the stage of testes
development and increase 15 days postpartum, commensurate with the start o
f seminiferous tubule fluid movement.