TY - JOUR
T1 - Expression of mouse IgA by transgenic mice, pigs and sheep
AU - Lo, David
AU - Pursel, Vernon
AU - Linton, Phyllis J.
AU - Sandgren, Eric
AU - Behringer, Richard
AU - Rexroad, Caird
AU - Palmiter, Richard D.
AU - Brinster, Ralph L.
PY - 1991/4
Y1 - 1991/4
N2 - The development of transgenic animal technology allows the introduction of desired traits into the germ line of mice and other animals. Since the production of antibody to various polysaccharide antigens can be protective against pathogenic bacteria, we generated transgenic mice, sheep and pigs carrying genes encoding the mouse α and χ chains for antibodies against phosphorylcholine (PC) to determine whether transgene antibody might be used to influence susceptibility to disease. High serum levels of mouse IgA were detected in transgenic mice and pigs but not in transgenic sheep. It has been noted that transgene immunoglobulin expression can suppress endogenous immunoglobulin gene rearrangement and expression, and indeed, in one mouse line, expression of the transgene resulted in < 10% of spleen B cells expressing endogenous IgM. Despite this suppression, significant levels of endogenous IgM were still secreted into the serum. Suppression of endogenous IgM expression was not seen in other mouse lines, nor was it seen in transgenic pigs. In the transgenic pigs, the mouse IgA was detected in the serum despite the absence of an intact mouse χ transgene, so the secreted antibody presumably included pig light chains. Little if any of the mouse IgA in these sera showed binding specificity for PC. In one of the founder sheep, mouse IgA was detectable in peripheral lymphocytes but not in serum. Mouse χ expression was not detected in the transgenic sheep harboring an intact χ transgene. These results illustrate the potential of introducing beneficial traits such as germ‐line‐encoded immunity into large mammalian species.
AB - The development of transgenic animal technology allows the introduction of desired traits into the germ line of mice and other animals. Since the production of antibody to various polysaccharide antigens can be protective against pathogenic bacteria, we generated transgenic mice, sheep and pigs carrying genes encoding the mouse α and χ chains for antibodies against phosphorylcholine (PC) to determine whether transgene antibody might be used to influence susceptibility to disease. High serum levels of mouse IgA were detected in transgenic mice and pigs but not in transgenic sheep. It has been noted that transgene immunoglobulin expression can suppress endogenous immunoglobulin gene rearrangement and expression, and indeed, in one mouse line, expression of the transgene resulted in < 10% of spleen B cells expressing endogenous IgM. Despite this suppression, significant levels of endogenous IgM were still secreted into the serum. Suppression of endogenous IgM expression was not seen in other mouse lines, nor was it seen in transgenic pigs. In the transgenic pigs, the mouse IgA was detected in the serum despite the absence of an intact mouse χ transgene, so the secreted antibody presumably included pig light chains. Little if any of the mouse IgA in these sera showed binding specificity for PC. In one of the founder sheep, mouse IgA was detectable in peripheral lymphocytes but not in serum. Mouse χ expression was not detected in the transgenic sheep harboring an intact χ transgene. These results illustrate the potential of introducing beneficial traits such as germ‐line‐encoded immunity into large mammalian species.
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U2 - 10.1002/eji.1830210421
DO - 10.1002/eji.1830210421
M3 - Article
C2 - 2019284
AN - SCOPUS:0025877015
SN - 0014-2980
VL - 21
SP - 1001
EP - 1006
JO - European Journal of Immunology
JF - European Journal of Immunology
IS - 4
ER -