pressed in certain genetic backgrounds, is under 
investigation. 
Dr. Leder is also John Emory Andrus Professor 
of Genetics at Harvard Medical School. 
Books and Chapters of Books 
Cardiff, R.D., Ornitz, D., Lee, F., Moreadith, R., 
Sinn, E., Muller, W., and Leder, P. 1992. Mam- 
mary morphogenesis and oncogenes. In Breast 
Cancer: Biological and Clinical Progress (Do- 
gliotti, L., Sapino, A., and Bussolati, G., Eds.). Bos- 
ton, MA: Kluwer Academic, pp 41-55. 
Leder, P. 1991 . Genetically engineered animals. In 
New Technologies and the Future of Food and 
Nutrition (Gaull, G.E., Ed.). New York: Wiley, 
pp 49-53. 
Articles 
Baetscher, M., Schmidt, E., Shimizu, A., Leder, P., 
and Fishman, M.C. 1991. SV40 T antigen trans- 
forms calcitonin cells of the thyroid but not 
CGRP-containing neurons in transgenic mice. 
Oncogene 6: 1 1 33-1 1 38. 
Cardiff, R.D., Sinn, E., Muller, W., and Leder, P. 
1991. Transgenic oncogene mice. Tumor pheno- 
type predicts genotype. Am J Pathol 139:495- 
501. 
Jackson-Grusby, L., Kuo, A., and Leder, P. 1992. A 
variant limb deformity transcript expressed in 
the embryonic mouse limb defines a novel for- 
min. Genes Dev 6:29-57 ■ 
Kwan, H., Pecenka, V., Tsukamoto, A., Parslow, 
T.G., Guzman, R., Lin, T.-P., Muller, W.J., Lee, 
F.S., Leder, P., and Varmus, H.E. 1992. Trans- 
genes expressing the Wnt-1 and int-2 proto- 
oncogenes cooperate during mammary carcino- 
genesis in doubly transgenic mice. Mol Cell Biol 
12:147-154. 
Morrison, B.W. and Leder, P. 1992. A receptor bind- 
ing domain of mouse interleukin-4 defined by a 
solid-phase binding assay and in vitro mutagene- 
sis. J Biol Chem 267:11957-11963. 
Ornitz, D.M., Cardiff, R D , Kuo, A., and Leder, P. 
1992. Int-2, an autocrine and/or ultra-short-range 
effector in transgenic mammary tissue trans- 
plants. /iV«?/ Cancer Inst 84:887-892. 
Ornitz, D.M., Yayon, A., Flanagan, J.G., Svahn, 
CM., Levi, E., and Leder, P. 1992. Heparin is 
required for cell-free binding of basic fibroblast 
growth factor to a soluble receptor and for mito- 
genesis in whole cells. Mol Cell Biol 12:240- 
247. 
Sussman, D.J., Chung, J., and Leder, P. 1991. In 
vitro and in vivo analysis of the c-myc RNA poly- 
merase. Nucleic Acids Res 19:5045-5052. 
Tepper, R.I., Coffman, R.L., and Leder, P. 1992. An 
eosinophil-dependent mechanism for the antitu- 
mor effect of interleukin-4. Science 257:548- 
551. 
Tutrone, R.F., Ball, R.A., Ornitz, D.M., Leder, P., 
and Richie, J. P. 1991. Benign prostatic hyperpla- 
sia in a transgenic mouse: a hormonally respon- 
sive investigatory model. Surg Forum 42:697- 
700. 
Vasicek, T.J., Levinson, D.A., Schmidt, E.V., Cam- 
pos-Torres, J., and Leder, P. 1992. B-less: a 
strain of profoundly B cell-deficient mice ex- 
pressing a human lambda transgene. / Exp Med 
175:1169-1180. 
Vogt, T.F., Jackson-Grusby, L., Wynshaw-Boris, 
A.J., Chan, D.C. and Leder, P. 1992. The same 
genomic region is disrupted in two transgene-in- 
duced limb deformity alleles. Mamm Genome 
3:431-437. 
MODELS AND APPROACHES FOR SOMATIC GENE THERAPY 
FredD. Ledley, M.D., Assistant Investigator 
During the past year Dr. Ledley's laboratory has 
advanced the characterization of methylmalonyl- 
CoA (coenzyme A) mutase deficiency and has 
moved to animal models in the development of 
methods for gene therapy of this deficiency state. 
The laboratory has also embarked in two new direc- 
tions aimed at establishing novel applications of 
gene therapy for congenital hypothyroidism and 
arthritis. 
Mutations, Structure, and Function 
in Methylmalonyl CoA Mutase 
In continuing studies of methylmalonyl-CoA mu- 
tase (MCM), a series of mutations have been identi- 
fied in cell lines that exhibit an intermediate form of 
the deficiency state, one partially remediated by ad- 
ministration of pharmacological levels of the hy- 
droxylcobalamin cofactor. These cell lines are also 
unique in that they participate in interallelic com- 
GENETICS 219 
