Efficient human IFN-gamma expression in the mammary gland of transgenic mice.
Two hybrid genes (BLG-HuIFN-gamma2 and BLG-HuIFN-gamma3) were constructed on the basis of sheep beta-lactoglobulin (BLG) and human interferon-gamma (HuIFN-gamma) gene sequences. They were used to direct HuIFN-gamma synthesis in the mammary gland of transgenic mice. HuIFN-gamma was efficiently produced in the mammary gland of transgenic mice. BLG-HuIFN-gamma2 transgenic females expressed HuIFN-gamma in the milk at concentrations up to 570 mg/ml, and BLG-HuIFN-gamma3 transgenic females expressed up to 350 mg/ml. All females carrying the BLG-HuIFN-gamma3 gene expressed HuIFN-gamma in their milk. No significant changes were observed in the HuIFN-gamma expression level during the lactation period. Using RT-PCR analysis, ectopic expression for both hybrid genes was found in transgenic mice. Despite ectopic expression of HuIFN-gamma in transgenic mice, their development and pregnancy were normal. The heritability of the HuIFN-gamma expression level in milk was demonstrated up to the F2 generation. This work demonstrates that hybrid genes have the potential to develop in transgenic domestic animals producing HuIFN-gamma in milk.
Lagutin
O V
OV
Shemyakin Institute of Bioorganic Chemistry, Russian Academy of Sciences, Moscow.
Dobrovolsky
V N
VN
Vinogradova
T V
TV
Kyndiakov
B N
BN
Khodarovich
Y M
YM
Jenkins
N
N
James
D
D
Markham
N
N
Larionov
O A
OA
D000818:Animals; D005260:Female; D005786:Gene Expression Regulation / Q000502:physiology*; D006801:Humans; D006824:Hybridization, Genetic; D007371:Interferon-gamma / Q000235:genetics*; D007782:Lactoglobulins / Q000235:genetics*; D008321:Mammary Glands, Animal / Q000378:metabolism*; D051379:Mice; D008822:Mice, Transgenic; D008892:Milk / Q000737:chemistry; D020133:Reverse Transcriptase Polymerase Chain Reaction
D007782:Lactoglobulins; D007371:Interferon-gamma