ArticleTransgenic research2004
Complementation of alpha-thalassaemia in alpha-globin knockout mice with a 191 kb transgene containing the human alpha-globin locus.
Article in Transgenic research, 2004. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.
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Who cites it
5 citing papers in PubMed, 12 citations in OpenAlex.
- Genetic polymorphisms among C57BL/6 mouse inbred strains.Transgenic research · 2011Article
- Integration of functional bacterial artificial chromosomes into human cord blood-derived multipotent stem cells.Gene therapy · 2009Article
- Position independent and copy-number-related expression of the bovine neonatal Fc receptor alpha-chain in transgenic mice carrying a 102 kb BAC genomic fragment.Transgenic research · 2007Article
- A 191-kb genomic fragment containing the human alpha-globin locus can rescue alpha-thalassemic mice.Mammalian genome : official journal of the International Mammalian Genome Society · 2005Article
- Role of transcription factors C/EBPalpha and PU.1 in normal hematopoiesis and leukemia.International journal of hematology · 2005Review
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
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 heterozygous mice and significantly normalised other haematological parameters. Interestingly the human transgene also induced a significant increase in red cell production and haematocrit above wild type values. This is the first report demonstrating complementation of a murine alpha-globin KO mutation by human alpha-globin gene expression from an intact human alpha-globin locus. The transgenic mouse model described in this report should be very useful for the study of human alpha-globin gene regulation and for the development of strategies to down regulate alpha-globin production as a means of ameliorating the severity of beta-thalassaemia.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.