The human immunodeficiency virus long terminal repeat is preferentially expressed in Langerhans cells in transgenic mice.
Four lines of transgenic mice containing the HIV LTR linked to the bacterial gene encoding chloramphenicol acetyltransferase (CAT) were constructed. In each line, a characteristic tissue pattern of CAT expression was observed with detectable levels present in the eye, heart, spleen, thymus, and tail. Low levels of CAT were present in circulating lymphocytes, but CAT activity in these cells could be augmented following treatment with the mitogen phytohemagglutinin (PHA). Likewise, CAT expression was present at only low levels in circulating monocytes, but higher levels of CAT were observed in macrophages grown in the presence of various cytokines (CSF-1, GM-CSF, IL-1 alpha, IL-4, and IL-2). Furthermore, Langerhans cells recovered from skin showed higher levels of CAT activity than those observed in other cells of monocyte-macrophage lineage. These results indicate that LTR-CAT expression in cells of monocyte-macrophage lineage may increase in proportion to the degree of differentiation of these cells. These animals may be useful in the study of cell-specific determinants of LTR-directed gene activity and may serve to identify exogenous cofactors that promote the progression of HIV-related disease in vivo.
Leonard
J
J
Laboratory of Molecular Microbiology, National Institutes of Health, Bethesda, MD 20892.
Khillan
J S
JS
Gendelman
H E
HE
Adachi
A
A
Lorenzo
S
S
Westphal
H
H
Martin
M A
MA
Meltzer
M S
MS
D000818:Animals; D015500:Chloramphenicol O-Acetyltransferase / Q000096:biosynthesis* / Q000235:genetics; D015696:Gene Products, tat; D006678:HIV / Q000235:genetics*; D007801:Langerhans Cells / Q000378:metabolism*; D008264:Macrophages / Q000276:immunology; D051379:Mice; D008822:Mice, Transgenic; D012091:Repetitive Sequences, Nucleic Acid; D013601:T-Lymphocytes / Q000276:immunology; D014157:Transcription Factors / Q000502:physiology; D054322:tat Gene Products, Human Immunodeficiency Virus
D015696:Gene Products, tat; D014157:Transcription Factors; D054322:tat Gene Products, Human Immunodeficiency Virus; D015500:Chloramphenicol O-Acetyltransferase