Organic anion-transporting polypeptide 1c1 (Oatp1c1) (also known as Slco1c1 and 
Oatp14) belongs to the family of Oatp and has been shown to facilitate the 
transport of T(4). In the rodent brain, Oatp1c1 is highly enriched in capillary 
endothelial cells and choroid plexus structures where it may mediate the entry 
of T(4) into the central nervous system. Here, we describe the generation and 
first analysis of Oatp1c1-deficient mice. Oatp1c1 knockout (KO) mice were born 
with the expected frequency, were not growth retarded, and developed without any 
overt neurological abnormalities. Serum T(3) and T(4) concentrations as well as 
renal and hepatic deiodinase type 1 expression levels were indistinguishable 
between Oatp1c1 KO mice and control animals. Hypothalamic TRH and pituitary TSH 
mRNA levels were not affected, but brain T(4) and T(3) content was decreased in 
Oatp1c1-deficient animals. Moreover, increased type 2 and decreased type 3 
deiodinase activities indicate a mild hypothyroid situation in the brain of 
Oatp1c1 KO mice. Consequently, mRNA expression levels of gene products 
positively regulated by T(3) in the brain were down-regulated. This central 
nervous system-specific hypothyroidism is presumably caused by an impaired 
passage of T(4) across the blood-brain barrier and indicates a unique function 
of Oatp1c1 in facilitating T(4) transport despite the presence of other thyroid 
hormone transporters such as Mct8.