The National Institute of Diabetes & Digestive & Kidney Diseases

Scientific Milestones

Important Years

1982 Isolation of mammary specific mRNAs
1984 Cloning of milk protein genes
1987 Discovery and characterization of transcription complexes on the HCMV-IE1 enhancer
1987 Development of the mammary gland bioreactor: first mouse to express a human pharmaceutical protein in its milk
1988 Discovery that hormonal regulation of milk protein gene expression is mediated by promoter elements
1992 First transgenic pig to express a foreign protein in its milk
1994 Establishment of the tetracycline regulated gene expression system in transgenic mice
1996 Verification of the multi hit theory during tumor progression
1997 Discovery that mammary development and function depends on the Stat5a transcription factor
1997 Targeting the Cre-lox recombination system to the mammary gland
1998 Discovering a role of C/EBPbeta signaling in the mammary development
1999 Deletion of the Brca1 gene from mammary epithelium using Cre-loxP recombination
2000 Bcl-x is required for the survival of fetal germ cells and mature erythrocytes, but not immature ones
2001 Bcl-x is required for controlled remodeling of mammary tissue
2001 Stat5 is required for the proliferation and differentiation of mammary epithelial cells (Miyoshi)
2002 Jak2 is required for pregnancy-mediated development of mammary epithelial cells
2002 Beta-catenin expression determines mammary epithelial cell identity
2002 Id2 is required for development of mammary epithelial cells at pregnancy
2002 Signaling via the IL6/gp130 pathway is important for mammary gland involution
2003 The characterization of protein markers for the analysis of mammary epithelial cell development
2004 Complete and cell-specific inactivation of the mouse Stat5 locus (Cui)
2006 Redefining the role of Stat5 in lymphoid development (Yao)
2006 Notch-RBPJ signaling defines cell lineages in mammary development (Buono)

Most Frequently Cited Papers from LGP: the >100 club

Furth et al.(1994) Temporal control of gene expression in transgenic mice by a tetracycline responsive promoter. Proc. Natl. Acad. Sci. U.S.A. 91, 9302-9306 (>460 times).

Liu et al. (1997) Stat5a is mandatory for adult mammary gland development and lactogenesis. Genes & Development 11, 179-186 (>350 times).

Liu et al. (1995) Cloning and expression of Stat5 and an additional homolog (Stat5b) involved in prolactin signal-transduction in mouse mammary tissue. Proc. Natl. Acad. Sci. USA 92, 8831-8835 (>280 times).

McKnight et al. (1992) Matrix attachment regions impart position independent regulation of a tissue specific gene in transgenic mice. Proc. Natl. Acad. Sci. U.S.A. 89, 6943-6947 (>210 times).

Hennighausen and Lubon (1987) Protein-DNA interaction in vitro. Methods Enzymol. 152, 721-735 (>180 times).

Hennighausen, L. and Robinson, G.W. (1998) Think globally, act locally: the making of a mammary gland. Genes and Development 12, 449-455 (>150 times)

Ewald et al. (1996) Time-sensitive reversal of hyperplasia in transgenic mice expressing SV40 T antigen. Science 273, 1384-1386 (>140).

Gordon et al. (1987) Production of human tissue plasminogen activator in transgenic mouse milk. Bio/Technology 5, 1183-1187 (>130 times).

Pittius et al.(1988a) A milk protein gene promoter directs the expression of human tissue plasminogen activator to the mammary gland in transgeni mice. Proc. Natl. Acad. Sci. USA 85, 5874-5878 (>130 times).

Liu et al. (1996) Activation of Stat5a And Stat5b by Tyrosine Phosphorylation Is Tightly Linked to Mammary Gland Differentiation. Mol. Endocrinology 10, 1496-1506 (>>130 times).

Campbell et al. (1984) Comparison of the whey acidic protein genes in rat and mouse. Nucleic Acids Res. 12, 8685-8697 (>130 times).

Wagner et al. (1997) Cre-mediated gene deletion in the mammary gland. Nucleic Acids Res. 1997 Nov 1;25(21):4323-30 (>130 times).

Robinson et al. (1995) Mammary epithelial cells undergo differentiation in cycling virgins but require pregnancy for the establishment of terminal differentiation. Development 121, 2079-2090 (>140 times).

Hennighausen, L.G. and Sippel, A.E. (1982) The mouse whey acidic protein is a novel member of the family of 'four-disulfide-core' proteins. Nucleic Acids Res. 10, 2677-2684 (>120 times).

Hennighausen, L.G. and Robinson, G.W. (2001)Developmental Cell (>120 times).

Robinson, G.W., Johnson, P.F., Hennighausen, L. and Sterneck, E.(1998) The C/EBP? transcription factor regulates epithelial cell proliferation and differentiation in the mammary gland. Genes and Development 12, 1907-1916. (>110 times).

Hennighausen and Fleckenstein (1986) Nuclear factor-1 interacts with 5 DNA elements in the promoter region of the human cytomegalovirus immediate early gene promoter. EMBO J. 5, 1367-1371 (>110 times).

Ghazal et al. (1987) Binding of transcription factors and the creration of a large nucleoprotein complex on the human cytomegalovirus enhancer. Proc. Natl. Acad. Sci. U.S.A. 84, 3658-3662 (>110 times).

Wall et al. (1991) High-level synthesis of a heterologous milk protein in the mammary glands of transgenic swine. Proc. Natl. Acad. Sci. USA 88, 1696-1700 (>100 times).

Hennighausen, L.G. & Sippel, A.E. (1982) Characterization and cloning of the messenger RNAs specific for the lactating mouse mammary gland. Eur. J. Biochem. 125, 131-141 (>100 times).

Burdon et al. (1991) Expression of a whey acidic protein transgene during mammary development. J. Biol. Chem. 266, 6909-6914 (>100 times).