P. Dickie et al., MYOPATHY AND SPONTANEOUS PASTEURELLA PNEUMOTROPICA-INDUCED ABSCESS FORMATION IN AN HIV-1 TRANSGENIC MOUSE MODEL, Journal of acquired immune deficiency syndromes and human retrovirology, 13(2), 1996, pp. 101-116
In an effort to augment human immunodeficiency virus type 1 (HIV-1) ge
ne expression in transgenic mice, an infectious proviral DNA clone was
modified by deleting the two NF kappa B binding sites and some adjace
nt upstream LTR sequences and replacing them with the core enhancer of
Moloney murine leukemia virus (MLV). Two independent lines of MLV/HIV
transgenic mice were established that expressed HIV-1-specific RNA in
lymphoid tissue, striated skeletal muscle, and the eye lens. Heterozy
gous animals from each transgenic line spontaneously developed an infl
ammatory disease of the eye associated with the production of copious
amounts of purulent lacrimal secretions beginning at 2 weeks of age. P
eriorbital abscess formation became grossly apparent by 2 months of ag
e and Pasteurella pneumotropica was cultured from the harderian glands
and conjunctival surfaces of many of the MLV/HIV animals but not thei
r nontransgenic, cohabiting littermates. This gram-negative commensal
bacterium has been previously associated with a similar disease phenot
ype in immunocompromised (e.g., nude mice) rodent colonies. MLV/HIV mi
ce developed normally until 15 weeks of age, when weight loss and wast
ing occurred, culminating in premature death (as earlier as 6 months o
f age). The cachexia was associated with an initially focal and subseq
uently progressive myopathy, coinciding with age-related increases of
HIV gene expression in muscle.