The human βE-globin gene from HbE(β26 Glu→Lys,G→A)homozygote,a commonhemoglobinopathy in China,was injected into the pronuclei of fertilized mouse eggs to prepare transgenicmice.A transgenic mouse bearing 16 copie...The human βE-globin gene from HbE(β26 Glu→Lys,G→A)homozygote,a commonhemoglobinopathy in China,was injected into the pronuclei of fertilized mouse eggs to prepare transgenicmice.A transgenic mouse bearing 16 copies of construct 5’HS2βE has characteristics of typical transgenicmice.It has been verified that the presence of erythroid enhancer 5’HS2 is necessary for the high level ex-pression of human βE-globin gene in transgenic mice,indicating that the cis-element 5’HS2 is effective for ab-normal β-globin gene as well.Although the expression level of β-globin gene was copy number-dependent asreported in previous studies,the average expression level per gene copy(12.1%)in transgenic mice bearingmany copies of 5’HS2βE(16 copies)was significantly lower than that(79.7%)in transgenic mice bearingfewer copies of the gene(2 copies).The possible mechanisms for this decrease of expression are discussed.Novel hemoglobin tetramers which presumably consist of human βE-globin chains and mouse endogenous α-globin chains have been assembled in transgenic mice.展开更多
基金the Chinese National High Technology Development Program (863-102-17-2)Cheng Scholarship,and Star Foundation of UCSF School of Medicine
文摘The human βE-globin gene from HbE(β26 Glu→Lys,G→A)homozygote,a commonhemoglobinopathy in China,was injected into the pronuclei of fertilized mouse eggs to prepare transgenicmice.A transgenic mouse bearing 16 copies of construct 5’HS2βE has characteristics of typical transgenicmice.It has been verified that the presence of erythroid enhancer 5’HS2 is necessary for the high level ex-pression of human βE-globin gene in transgenic mice,indicating that the cis-element 5’HS2 is effective for ab-normal β-globin gene as well.Although the expression level of β-globin gene was copy number-dependent asreported in previous studies,the average expression level per gene copy(12.1%)in transgenic mice bearingmany copies of 5’HS2βE(16 copies)was significantly lower than that(79.7%)in transgenic mice bearingfewer copies of the gene(2 copies).The possible mechanisms for this decrease of expression are discussed.Novel hemoglobin tetramers which presumably consist of human βE-globin chains and mouse endogenous α-globin chains have been assembled in transgenic mice.
