S. Raguz et al., MUSCLE-SPECIFIC LOCUS-CONTROL REGION ACTIVITY ASSOCIATED WITH THE HUMAN DESMIN GENE, Developmental biology (Print), 201(1), 1998, pp. 26-42
We describe the reproduction of the full pattern of expression of the
muscle-specific desmin gene in transgenic mice using a 240-kb genomic
clone spanning the human desmin locus. Analysis of RNA from adult tiss
ues demonstrated that this fragment possesses all the necessary geneti
c regulatory elements required to provide reproducible, site-of-integr
ation-independent, physiological levels of tissue-specific expression
that is directly proportional to transgene copy number in all muscle c
ell types. In situ hybridization revealed that in marked contrast to m
urine desmin which is strongly expressed in the myotome of the somites
, skeletal muscles, the heart, and smooth muscle of the vasculature by
9.5 days postcoitum, human desmin transgene expression was completely
absent from smooth muscles, was very weak and restricted to the atriu
m and outflow tract within the heart, and was expressed at only 5% of
murine desmin mRNA levels within the myotome of the somites. The spati
al distribution and levels of human and mouse desmin expression were n
ot coincident until 14.5 days postcoitum. Immunohistochemical analysis
of human embryos at comparable stages of development showed that this
transgene faithfully reproduces the human and not the mouse developme
ntal expression pattern for this gene in transgenic mice. These result
s indicate that the 240-kb desmin genomic clone is capable of establis
hing an independent, chromatin domain in transgenic mice and provides
the first definitive data for muscle-specific locus control region act
ivity. In addition, our results demonstrate that the behavior of human
transgenes in mice should, whenever possible, be compared to expressi
on patterns for that gene in human embryonic as well as adult tissues.
(C) 1998 Academic Press.