title: Renal imino acid and glycine transport system ontogeny and involvement in developmental iminoglycinuria.
abstract: Renal maturation occurs post-natally in many species and reabsorption capacity at birth can vary substantially from the mature kidney. However, little is known regarding the maturation of amino acid transport mechanisms, despite the well-known physiological state of developmental iminoglycinuria. Commonly seen during early infancy, developmental iminoglycinuria is a transient version of the persistent inherited form of the disorder, referred to as iminoglycinuria, and manifests as a urinary hyperexcretion of proline, hydroxyproline and glycine. The transporters involved in developmental iminoglycinuria and their involvement in the improvement of renal reabsorption capacity remain unknown. qPCR (quantitative real-time PCR) and Western blot analysis in developing mouse kidney revealed that the expression of Slc6a18, Slc6a19, Slc6a20a and Slc36a2 was lower at birth (approx. 3.4-, 5.0-, 2.4- and 3.0-fold less than adult kidney by qPCR respectively) and increased during development. Furthermore, immunofluorescence confocal microscopy demonstrated the absence of apical expression of Slc6a18, Slc6a19, Slc6a20a and the auxiliary protein collectrin in kidneys of mice at birth. This correlated with the detection of iminoglycinuria during the first week of life. Iminoglycinuria subsided (proline reduction preceded glycine) in the second week of life, which correlated with an increase in the expression of Slc6a19 and Slc6a20a. Mice achieved an adult imino acid and glycine excretion profile by the fourth week, at which time the expression level of all transporters was comparable with adult mice. In conclusion, these results demonstrate the delayed expression and maturation of Slc6a18, Slc6a19, Slc6a20a and Slc36a2 in neonatal mice and thus the molecular mechanism of developmental iminoglycinuria.
authors.affiliation: Gene and Stem Cell Therapy Programme, Centenary Institute, Missenden Road, Camperdown, New South Wales 2050, Australia.
authors.forename: Jessica M
authors.initials: JM
authors.lastname: Vanslambrouck
authors.forename: Angelika
authors.initials: A
authors.lastname: Bröer
authors.forename: Thuvaraka
authors.initials: T
authors.lastname: Thavyogarajah
authors.forename: Jeff
authors.initials: J
authors.lastname: Holst
authors.forename: Charles G
authors.initials: CG
authors.lastname: Bailey
authors.forename: Stefan
authors.initials: S
authors.lastname: Bröer
authors.forename: John E J
authors.initials: JE
authors.lastname: Rasko
mesh_terms: D000592:Amino Acid Metabolism, Inborn Errors / Q000235:genetics / Q000378:metabolism*; D026921:Amino Acid Transport Systems, Neutral / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D001692:Biological Transport; D005998:Glycine / Q000378:metabolism* / Q000652:urine; D007098:Imino Acids / Q000378:metabolism* / Q000652:urine; D007668:Kidney / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D008856:Microscopy, Fluorescence; D014982:Xenopus laevis
chemical_list: D026921:Amino Acid Transport Systems, Neutral; D007098:Imino Acids; C033013:iminoglycine; D005998:Glycine