Dr. Lalouel is also Professor of Human Genetics 
at the University of Utah School of Medicine. 
Books and Chapters of Books 
Lalouel, J. -M. 1992. Linkage analysis in human ge- 
netics. In Plant Genomes: Methods for Genetic 
and Physical Mapping (Beckman, J.S., and Os- 
born, T.C., Eds.). Dordrecht: Kluwer Academic, 
pp 167-180. 
Williams, R.R., Hunt, S.C., Hasstedt, S.J., Hopkins, 
P.N., Wu, L.L., Schumacher, M.C., Berry, T.D., 
Stults, B.M., Barlow, G.K., Lifton, R.P., and 
Lalouel, J.-M. 1991. A population perspective 
for genetics research and applications to control 
cardiovascular disease in Utah. In Genetic Ap- 
proaches to Coronary Heart Disease and Hyper- 
tension (Berg, K., Bulyzhenkov, V., Christen, Y., 
and Corvol, P., Eds.). New York: Springer-Verlag, 
pp 8-19. 
Articles 
Dumanski, J. P., Carlbom, E., Collins, V.P., Nor- 
denskjold, M., Emanuel, B.S., Budarf, M.L., 
McDermid, HE., Wolflf, R., O'Connell, P., 
White, R.L., Lalouel, J.-M., and Leppert, M. 
1991. A map of 22 loci on human chromosome 
22. Genomics 11:709-719- 
Emi, M., Hegele, R.M., Hopkins, P.N., Wu, L.L., 
Plaetke, R., Williams, R.R., and Lalouel, J.-M. 
1991. Effects of three genetic loci in a pedigree 
with multiple lipoprotein phenotypes. Arterio- 
scler Thromb 5:1349-1355. 
Hopkins, P.N., Wu, L.L., Schumacher, M.C., Emi, M., 
Hegele, R.M., Hunt, S C., Lalouel, J.-M., and Wil- 
liams, R.R. 1991. Type III dyslipoproteinemia in 
patients heterozygous for familial hypercholes- 
terolemia and apolipoprotein E2. Evidence for 
a gene-gene interaction. Arterioscler Thromb 
5:1137-1146. 
Jeunemaitre, X., Lifton, R.P., Hunt, S.C., Williams, 
R.R., and Lalouel, J.-M. 1992. Absence of linkage 
between the angiotensin converting enzyme 
locus and human essential hypertension. Nature 
Genet 1:72-75. 
Lalouel, J.-M., Wilson, D.E., and Iverius, P.-H. 
1992. Lipoprotein lipase and hepatic triglyceride 
lipase: molecular and genetic aspects. Curr Opin 
Lipidol 3:86-95. 
Lifton, R.P., Dluhy, R.G. Powers, M., Rich, G.M., 
Cook, S., Ulick, S., and Lalouel, J.-M. 1992. A 
chimaeric 1 l|8-hydroxylase/aldosterone synthase 
gene causes glucocorticoid-remediable aldoste- 
ronism and human hypertension. Nature 355: 
262-265. 
GENETIC CONTROL OF CELL GROWTH AND DEVELOPMENT 
Philip Leder, M.D., Senior Investigator 
Dr. Leder and his colleagues are attempting to un- 
derstand mechanisms that control malignant cell 
growth. Specific attention this year has focused on 
the action of certain growth factors that can act as 
oncogenes and other factors (lymphokines) that can 
modulate tumorigenesis in the living organism. 
Much of this work involves the transgenic mouse as 
an experimental paradigm. 
Interleukin-4, a Biologic Regulator 
and Antitumor Agent 
Molecular and cellular interactions ofH-4. Dr. 
Leder and his colleagues have pursued two lines of 
investigation in order to understand the potent anti- 
tumor effect of the lymphokine IL-4. Several years 
ago they discovered (and described in an earlier re- 
port) this antitumor effect as an indirect or host- 
induced response. Having now devised a convenient 
solid-phase assay to assess the binding activity of 
IL-4 to its receptor, they were able to identify those 
amino acids and regions of the IL-4 molecule that 
are required for receptor-Iigand interaction. 
In a separate assay viewing the effects of IL-4 on 
the activation of T cells, they correlated the ob- 
served binding properties with the biologic activity 
of mutant ligand molecules. In so doing, they de- 
fined regions and amino acid residues of the human 
and mouse IL-4 molecules that are essential for 
species-specific binding. They also identified a spe- 
cific mutation capable of binding, but not of induc- 
ing, a biologic response. These studies put the evo- 
lutionary changes in the human and mouse IL-4 
molecules in a rational context and created an im- 
portant IL-4 mutant that can be used as a dominant 
negative for perturbing lL-4 function in vivo. 
The antitumor effect ofH-4 is eosinophil depen- 
dent. Inasmuch as the antitumor effect of IL-4 is 
mediated via a host response mechanism, it was of 
great interest to determine the cellular require- 
ments through which this effect operates. Making 
GENETICS 217 
