Correction of renal tubular acidosis in carbonic anhydrase II-deficient mice with gene therapy

The Journal of Clinical Investigation
L W LaiY H Lien

Abstract

Carbonic anhydrase II (CAII) deficiency in humans is associated with a syndrome of renal tubular acidosis, osteopetrosis, and cerebral calcification. A strain of mice of CAII deficiency due to a point mutation also manifests renal tubular acidosis. We report here that retrograde injection of cationic liposome complexed with a CAII chimeric gene, using a cytomegalovirus (CMV) promoter/enhancer as an expression cassette to drive human CAII cDNA, into the renal pelvis of CAII-deficient mice results in expression of CAII in the kidney. The levels of both the CAII gene and its corresponding mRNA were highest by day 3 after treatment, diminishing thereafter, but remaining detectable by 1 mo. After gene therapy, CAII-deficient mice restored the ability to acidify urine after oral administration of ammonium chloride. The ability to acidify urine was maintained at 3 wk after gene therapy, and was eventually lost by 6 wk. Immunohistochemistry studies using anti-CAII antibodies showed that CAII was expressed in tubular cells of the outer medulla and corticomedullary junction. The gene therapy was not associated with nephrotoxicity as assessed by blood urea nitrogen levels and renal histology. To our knowledge, this is the first successful...Continue Reading

References

Jul 22, 1991·Biochimica Et Biophysica Acta·W F BrechueT H Maren
Jun 1, 1989·BioEssays : News and Reviews in Molecular, Cellular and Developmental Biology·R E Tashian
Nov 1, 1987·Proceedings of the National Academy of Sciences of the United States of America·P L FelgnerM Danielsen
Mar 1, 1988·Proceedings of the National Academy of Sciences of the United States of America·S E LewisR E Tashian
Feb 1, 1980·Kidney International·G Lönnerholm, Y Ridderstråle
Oct 10, 1995·Proceedings of the National Academy of Sciences of the United States of America·A R ThierryL C Mahan
Dec 1, 1993·Proceedings of the National Academy of Sciences of the United States of America·G J NabelA E Chang
Mar 1, 1996·Human Gene Therapy·S F AliñoM Lejarreta
Oct 15, 1996·Proceedings of the National Academy of Sciences of the United States of America·C J WheelerS H Cheng
May 1, 1997·Gene Therapy·L W LaiY H Lien

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Citations

Jan 5, 2008·Calcified Tissue International·David S MargolisYeong-Hau H Lien
Jan 22, 2004·Biochemical and Biophysical Research Communications·S KamedaF Gejyo
Mar 22, 2005·The International Journal of Biochemistry & Cell Biology·Christopher M LaingRobert J Unwin
Nov 20, 1998·Current Opinion in Biotechnology·D SchermanJ Crouzet
Oct 30, 1998·Molecular Medicine Today·S YeE B Kmiec
Apr 7, 2012·Molecular Pharmaceutics·Wei-Hsien HsiehJiahorng Liaw
Nov 13, 2002·Kidney International·Chien-Te LeeYeong-Hau H Lien
Feb 14, 2002·Kidney International·Betsy C HeroldLisa M Satlin
Feb 14, 2002·Kidney International·G Luca GusellaMary E Klotman
Feb 14, 2002·Kidney International·Li-Wen Lai, Yeong-Hau H Lien
Feb 14, 2002·Kidney International·Alan S Verkman, Baoxue Yang
Feb 14, 2002·Kidney International·Ralph WitzgallNicholas Obermüller
Feb 28, 2002·Human Gene Therapy·Hiroki MaruyamaJun-Ichi Miyazaki
Nov 29, 2011·Brain : a Journal of Neurology·Thomas M BosleyKhaled K Abu-Amero
Feb 5, 2002·Annual Review of Physiology·Seth L Alper
Dec 29, 2011·Physiological Genomics·Alison J KriegelMingyu Liang
Jan 23, 2008·Cellular Physiology and Biochemistry : International Journal of Experimental Cellular Physiology, Biochemistry, and Pharmacology·Xuming SunSnezana Petrovic
Mar 15, 2005·American Journal of Respiratory and Critical Care Medicine·Pavlos M MyrianthefsJacob Iasha Sznajder
Mar 10, 2004·Internal Medicine·Enyu Imai, Yoshitaka Isaka
Dec 1, 2001·Expert Opinion on Biological Therapy·L W Lai, Y H Lien
Nov 4, 2000·Expert Opinion on Investigational Drugs·E Imai, Y Isaka
Jun 4, 2004·Expert Opinion on Biological Therapy·Yeong-Hau H Lien, Li-Wen Lai
Jul 6, 2010·Pharmacology & Therapeutics·José M López-NovoaFrancisco J López-Hernández
Jun 24, 2003·Journal of Bone and Mineral Research : the Official Journal of the American Society for Bone and Mineral Research·D L KollerM Peacock
Mar 1, 2009·Proteomics. Clinical Applications·Raymond TytherDavid Sheehan
Jul 6, 2004·Journal of Pharmacological and Toxicological Methods·Els A van der WoudenLeo E Deelman
Jun 24, 2014·Nanomedicine : Nanotechnology, Biology, and Medicine·Tomoaki KurosakiMitsuru Hashida
Feb 13, 2001·Annual Review of Medicine·D BatlleA Mitra
Feb 26, 2016·Genetics in Medicine : Official Journal of the American College of Medical Genetics·Carmen Diez-FernandezJohannes Häberle
Oct 30, 2001·Clinical Pediatrics·K S Roth, J C Chan
Jan 24, 2003·Magnetic Resonance in Medicine : Official Journal of the Society of Magnetic Resonance in Medicine·Natarajan RaghunandRobert J Gillies
Jul 11, 2006·American Journal of Physiology. Renal Physiology·Joris H RobbenPeter M T Deen
Apr 3, 2001·Nature Biotechnology·M C RiceE B Kmiec
Oct 10, 2002·American Journal of Physiology. Renal Physiology·Eitan Gross, Ira Kurtz
Sep 17, 2004·Human Cell·Keiichi ItoDiane Felsen
Jan 14, 1999·The American Journal of Physiology·V R Kelley, V P Sukhatme
Jun 1, 2001·Journal of the Royal Society of Medicine·R J Unwin, G Capasso
Apr 24, 2020·Molecular Diagnosis & Therapy·Jeffrey D Rubin, Michael A Barry
Mar 28, 2003·Journal of the American Society of Nephrology : JASN·Sifeng ChenC Craig Tisher
Aug 4, 1999·American Journal of Kidney Diseases : the Official Journal of the National Kidney Foundation·C ShayakulS L Alper

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