Expression of a foreign gene in cats reconstituted with retroviral vector infected autologous bone marrow.
A Moloney murine leukemia virus based retroviral vector was used to transfer the bacterial neomycin resistance gene (neoR) into feline hematopoietic cells. We reconstituted four cats that had been lethally irradiated with autologous bone marrow that had been infected with the N2 or SAX retroviral vector. Bone marrow cells from all four cats expressed the neoR gene 30 days posttransplant and three of four cats still had the neoR gene and a low level of drug resistant colony-forming unit granulocyte-macrophage after more than 200 days. Two of the four cats unexpectedly developed diabetes mellitus 90 days posttransplantation. The expression of a foreign gene in cats, albeit at a low level, demonstrates that retroviral vectors can be used for gene transfer in noninbred large animal species and may be useful for gene therapy of humans. The development of diabetes mellitus in two of the subjects emphasizes the value of animal models for the study of possible deleterious effects of retroviral vector-mediated gene transfer.
Lothrop
C D
CD
College of Veterinary Medicine, University of Tennessee, Knoxville 37901-1071.
al-Lebban
Z S
ZS
Niemeyer
G P
GP
Jones
J B
JB
Peterson
M G
MG
Smith
J R
JR
Baker
H J
HJ
Morgan
R A
RA
Eglitis
M A
MA
Anderson
W F
WF
D000818:Animals; D001483:Base Sequence; D001853:Bone Marrow / Q000382:microbiology*; D001854:Bone Marrow Cells; D016026:Bone Marrow Transplantation; D002415:Cats; D004279:DNA, Viral / Q000235:genetics; D003921:Diabetes Mellitus, Experimental / Q000235:genetics / Q000473:pathology; D005260:Female; D015870:Gene Expression; D005796:Genes / Q000235:genetics*; D015316:Genetic Therapy; D005822:Genetic Vectors; D006098:Granulocytes / Q000473:pathology / Q000502:physiology; D008264:Macrophages / Q000473:pathology / Q000502:physiology; D008297:Male; D051379:Mice; D008969:Molecular Sequence Data; D010957:Plasmids; D016133:Polymerase Chain Reaction; D012190:Retroviridae / Q000235:genetics*; D014182:Transplantation, Autologous
D004279:DNA, Viral