High impact information on Slc22a5

• Initially, we analysed the mouse gene and found a missense mutation in Slc22a5 in jvs mice [1].
• This study suggests that Octn2-type carnitine transporter is dysfunctional in hepatocytes of JVS mice [2].
• Organic cation/carnitine transporter OCTN2 (Slc22a5) is responsible for carnitine transport across apical membranes of small intestinal epithelial cells in mouse [3].
• Saturable uptake of carnitine was also confirmed in isolated enterocytes obtained from wild-type mice, and the Km value obtained (approximately 20 microM) was close to that reported for carnitine uptake by human embryonic kidney 293 cells stably expressing mouse OCTN2 (Slc22a5) [3].
• Octn1 and Octn2 mRNA expression was similar, with the highest levels in kidney followed by small intestine [4].

Biological context of Slc22a5

• Abnormal gene expression and regulation in the liver of jvs mice with systemic carnitine deficiency [5].
• This phenotype is caused by a missense mutation (Leu352Arg) of a sodium-dependent carnitine/organic cation transporter, Octn2 (Slc22a5) [6].
• Mapping of jvs (juvenile visceral steatosis) gene, which causes systemic carnitine deficiency in mice, on chromosome 11 [7].
• The jvs mouse could be a useful model for pharmacokinetics and drug metabolism studies concerning Octn2 substrate drugs [6].

Anatomical context of Slc22a5

• Zero-net-flux method analysis indicated higher in vivo recovery of ALCAR and lower physiological ALCAR concentration in thalamus extracellular fluid (ECF) in jvs mice compared with wild-type mice [8].

Associations of Slc22a5 with chemical compounds

• Carnitine-deficient jvs mice expressed reduced levels of a group of genes which are preferentially expressed in the liver, including urea cycle enzyme genes (Biochim. Biophys. Acta 1138, 167-171, 1992) [5].
• Externally added ALCAR showed significantly slower initial uptake across the BBB in jvs mouse [8].

Other interactions of Slc22a5

• On the other hand, GR protein accumulated in the nuclear fraction in jvs mice [5].
• The expression of alpha-fetoprotein and aldolase A was elevated, indicating that the liver of jvs mice is undifferentiated or dedifferentiated (FEBS Lett. 311, 63-66, 1992) [5].

References