Complementation of alpha-thalassaemia in alpha-globin knockout mice with a 191 kb transgene containing the human alpha-globin locus

Transgenic Research
Keith Al-HasaniPanayiotis A Ioannou

Abstract

alpha-thalassaemia is an inherited blood disorder caused by a decrease in the synthesis of alpha-globin due to mutations in one or both of the alpha-globin genes located on human chromosome 16. A 191 kb transgene derived from a sequenced bacterial artificial chromosome (BAC) clone carrying the human alpha-globin gene cluster, together with about 100 kb of sequence upstream of DNase1 hypersensitive site HS-40 and 30 kb downstream of the alpha1-globin gene, was introduced into fertilised mouse oocytes by pronuclear microinjection. Three transgenic founder mice were obtained. Analysis of one transmitting line by fluorescent in situ hybridisation and quantitative PCR demonstrated a single copy integration of the human alpha-globin transgene on chromosome 1. Analysis of haemoglobins from the peripheral blood by cellulose acetate electrophoresis and high performance liquid chromatography (HPLC) demonstrated synthesis of human alpha-globin to about 36% of the level of each mouse alpha-globin locus. Breeding of transgenic mice with mice heterozygous for a knockout (KO) deletion of both murine alpha-globin genes showed that the human alpha-globin locus restored haemoglobin levels and red cell distribution width to normal in double heter...Continue Reading

Citations

Nov 15, 2005·Mammalian Genome : Official Journal of the International Mammalian Genome Society·Keith Al-HasaniPanayiotis A Ioannou
May 28, 2010·Transgenic Research·Esther ZuritaLluís Montoliu
Jan 30, 2007·Nature Reviews. Immunology·Frank Rosenbauer, Daniel G Tenen
Oct 13, 2011·DNA and Cell Biology·Chiao-Ling LoAmy C Lossie
Apr 9, 2008·Current Opinion in Hematology·Douglas R Higgs, William G Wood
Sep 15, 2005·International Journal of Hematology·Steffen KoschmiederDaniel G Tenen
Nov 18, 2006·Blood Cells, Molecules & Diseases·Xiao-bin TangChih-Chuan Liang
Dec 13, 2005·Annals of the New York Academy of Sciences·D R HiggsR Gibbons
Apr 25, 2006·Genomics·Duangporn JamsaiPanayiotis A Ioannou

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