cules in transgenic mice as a means of producing 
models of liuman hemoglobinopathies. 
III. Megacolon in Mice Expressing /fox-i. 4. 
Hox-1.4, a member of the cluster of homeobox- 
containing genes on mouse chromosome 6, is ex- 
pressed almost exclusively in the testis of adult 
mice but is expressed in a number of organ systems 
during midgestation. This gene, like other 
homeobox-containing genes, is probably a tran- 
scription factor that regulates expression of other 
genes and possibly itself A marked version of the 
Hox-1.4 gene that would encode a functional Hox- 
1.4 protein but have an RNA transcript that could 
be identified was made in collaboration with Dr. 
Debra Wolgemuth (Columbia University). Several 
lines of transgenic mice expressed the marked Hox- 
1.4 gene in appropriate sites during embryogenesis 
(as revealed by in situ hybridization) and in the 
germ cells of the adult testis. These experiments in- 
dicate that the sequences necessary for cell-specific 
expression lie within the 7 kb of Hox-1.4 sequence 
that was tested. 
PUBLICATIONS 
The most remarkable effect of Hox-1.4 expres- 
sion in these transgenic mice is that the mice de- 
velop a condition known as megacolon. These mice 
have difficulty extruding feces; consequently the 
bowel becomes grossly distended, a condition that 
can cause death. This syndrome resembles that of 
two existing mouse strains and a congenital 
megacolon condition in humans known as 
Hirschsprung's disease. Megacolon is thought to be 
due to inadequate innervation of the distal portion 
of the colon by the enteric nervous system. The fact 
that Hox-1.4 is expressed abundantly in the mesen- 
chymal cells in the day 12.5 embryo suggests that 
the defect in these transgenic mice may lie in inap- 
propriate pathfinding signals elaborated by meso- 
dermal cells in the gut rather than a defect in the 
neural crest cells that migrate into the gut to form 
the enteric nervous system. These experiments pro- 
vide an unexpected molecular clue to the develop- 
ment of the enteric nervous system that has stimu- 
lated research in this area. 
Dr. Palmiter is also Professor of Biochemistry at 
the University of Washington. 
Books and Chapters of Books 
Filippi, E, Buras, J., McLachlan, A., Popper, H., Pinkert, C, Palmiter, R.D., Brinster, R.L., and Chisari, F.V 1988. 
Overproduction of the hepatitis B virus large envelope polypeptide causes filament storage, ground-glass- 
cell formation, hepatocellular injury, and nodular hyperplasia in transgenic mice. In Viral Hepatitis and 
Liver Disease. New York: Liss, pp 632-640. 
Pursel, VG., Miller, K.F., Bolt, D.J., Pinkert, C.A., Hammer, R.E. , Palmiter, R.D. , and Brinster, R.L. 1989. Inser- 
tion of growTih hormone genes into pig embryos. In Biotechnology in Growth Regulation (Heap, R.B., 
Prosser, C.G., and Lamming, G.E., Eds.). London: Butterworths, pp 181-188. 
Articles 
Braun, R.E., Behringer, R.R. , Peschon, J.J., Brinster, R.L., and Palmiter, R.D. 1989. Genetically haploid sperma- 
tids are phenotypically diploid. Nature 337:373-376. 
Braun, R.E., Peschon, J.J. , Behringer, R.R., Brinster, R.L., and Palmiter, R.D. 1989. Protamine 3 '-untranslated 
sequences regulate temporal translational control and subcellular localization of growth hormone in 
spermatids of transgenic mice. Genes Dev 3:793-802. 
Burkly, L.C., Lo, D., Cowing, C, Palmiter, R.D. , Brinster, R.L., and Flavell, R.A. 1989. Selective expression of 
class II E^'^ gene in transgenic mice. J Immunol 142:2081-2088. 
Doi, T, Striker, L.J., Quaife, C , Conti, E.G., Palmiter, R.D. , Behringer, R.R. , Brinster, R.L., and Striker, G.E. 
1988. Progressive glomerulosclerosis develops in transgenic mice chronically expressing growth hormone 
and grov^^h hormone releasing factor but not in those expressing insulin-like growth factor I. Am J Pathol 
131:398-403. 
Lo, D., Burkly L.C., Flavell, R.A. , Palmiter, R.D. , and Brinster, R.L. 1989. Tolerance in transgenic mice express- 
ing class II major histocompatibility complex on pancreatic acinar cells. J Exp Med 170:87-104. 
Continued 
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