Magnetic resonance evidence of hypoxia in a homozygous alpha-knockout of a transgenic mouse model for sickle cell disease

The Journal of Clinical Investigation
M E FabryR L Nagel

Abstract

All transgenic mouse models for sickle cell disease express residual levels of mouse globins which complicate the interpretation of experimental results. We now report on a mouse expressing high levels of human betaS and 100% human alpha-globin. These mice were created by breeding the alpha-knockout and the mouse beta(major)-deletion to homozygosity in mice expressing human alpha- and betaS-transgenes. These betaS-alpha-knockout mice have accelerated red cell destruction, altered hematological indices, ongoing organ damage, and pathology under ambient conditions which are comparable with those found in alphaH betaS-Ant[betaMDD] mice without introduction of additional mutations which convert betaS into a "super-betaS" such as the doubly mutated betaS-Antilles. This is of particular importance for testing strategies for gene therapy of sickle cell disease. Spin echo magnetic resonance imaging at room air and 100% oxygen demonstrated the presence of blood hypoxia (high levels of deoxygenated hemoglobin) in the liver and kidneys that was absent in control mice. We demonstrate here that transgenic mice can be useful to test new noninvasive diagnostic procedures, since the magnetic resonance imaging technique described here potential...Continue Reading

References

Dec 15, 1992·Proceedings of the National Academy of Sciences of the United States of America·M E FabryF Costantini
Dec 15, 1992·Proceedings of the National Academy of Sciences of the United States of America·M E FabryR L Nagel
Feb 1, 1991·The Journal of Clinical Investigation·E M RubinS M Clift
Feb 2, 1990·Science·T M RyanR R Behringer
Apr 1, 1990·Magnetic Resonance in Medicine : Official Journal of the Society of Magnetic Resonance in Medicine·S OgawaP Glynn
Jan 11, 1990·Nature·D R GreavesF Grosveld
Dec 1, 1986·Proceedings of the National Academy of Sciences of the United States of America·N MonplaisirJ Rosa
Oct 1, 1984·Kidney International·M BrezisF H Epstein
Sep 26, 1995·Proceedings of the National Academy of Sciences of the United States of America·D J CiavattaT M Townes
Mar 9, 1995·The New England Journal of Medicine·M Brezis, S Rosen
Jun 1, 1994·Magnetic Resonance in Medicine : Official Journal of the Society of Magnetic Resonance in Medicine·R T ConstableJ C Gore
Jan 1, 1994·Magnetic Resonance in Medicine : Official Journal of the Society of Magnetic Resonance in Medicine·R P KennanJ C Gore
Dec 5, 1995·Proceedings of the National Academy of Sciences of the United States of America·B YangO Smithies
Jul 1, 1996·Kidney International·N BankR L Nagel

❮ Previous
Next ❯

Citations

Mar 2, 1999·Microvascular Research·H ZoellnerB R Binder
Jan 15, 1995·Journal of Biotechnology·M G Solis-RecendezM Maugras
Mar 11, 1994·Toxicology·B el AzzouziY Thomas
Jan 5, 1996·Early Human Development·M MinamitaniY Suzuki
Nov 26, 2003·Blood Cells, Molecules & Diseases·Anne C RybickiRonald L Nagel
Oct 23, 2004·Best Practice & Research. Clinical Haematology·Michel SadelainIsabelle Rivière
Aug 5, 1998·Brain Research·B Y AzizehC W Cotman
Nov 24, 2001·Clinica Chimica Acta; International Journal of Clinical Chemistry·H J NaH M Kim
Jun 11, 1998·International Journal of Gynaecology and Obstetrics : the Official Organ of the International Federation of Gynaecology and Obstetrics·H R MaranaS P Cunha
Oct 2, 1998·Thrombosis Research·H ZoellnerB Binder
Oct 31, 1998·Brain Research. Molecular Brain Research·A SalminenT Suuronen
Nov 1, 1996·International Journal of Radiation Oncology, Biology, Physics·C M GajdusekM R Mayberg
Mar 14, 2000·Hearing Research·S A AlamT Takasaka
Dec 2, 1999·Alcohol·B L McVicker, C A Casey
Aug 11, 2001·Free Radical Biology & Medicine·U JungA S Chung
Dec 1, 1996·Current Opinion in Cell Biology·T S Zorick, G Lemke
Oct 4, 2000·The Journal of Heart and Lung Transplantation : the Official Publication of the International Society for Heart Transplantation·P AnversaJ Kajstura
Dec 9, 1998·Proceedings of the National Academy of Sciences of the United States of America·J C ChangK M Gaensler
Apr 23, 2002·Journal of Biomedical Optics·Richard P Kennan, Kevin L Behar
Nov 10, 2001·Annual Review of Biomedical Engineering·T F BudingerA P Koretsky
Oct 12, 2013·Néphrologie & thérapeutique·Maud CazenaveVincent Audard
Jun 18, 2002·Blood Cells, Molecules & Diseases·Jessica Ieremia, C Anthony Blau
Sep 25, 2016·American Journal of Kidney Diseases : the Official Journal of the National Kidney Foundation·Jean-François DeuxPablo Bartolucci
Feb 13, 2001·British Journal of Haematology·R L Nagel, M E Fabry
Mar 9, 2004·Magnetic Resonance in Medicine : Official Journal of the Society of Magnetic Resonance in Medicine·Richard P KennanMary E Fabry
Oct 6, 2005·NMR in Biomedicine·Brian J NiemanR Mark Henkelman
Jan 26, 2000·Development, Growth & Differentiation·T YoshimizuY Matsui
Nov 25, 2003·Hematology·George F AtwehRobert J Adams
May 23, 2000·Journal of the American Society of Nephrology : JASN·Militza KiroychevaNorman Bank
Nov 5, 1997·Science·T M RyanT M Townes

❮ Previous
Next ❯

Related Concepts

Related Feeds

Anemia

Anemia develops when your blood lacks enough healthy red blood cells. Anemia of inflammation (AI, also called anemia of chronic disease) is a common, typically normocytic, normochromic anemia that is caused by an underlying inflammatory disease. Here is the latest research on anemia.

Blood And Marrow Transplantation

The use of hematopoietic stem cell transplantation or blood and marrow transplantation (bmt) is on the increase worldwide. BMT is used to replace damaged or destroyed bone marrow with healthy bone marrow stem cells. Here is the latest research on bone and marrow transplantation.