Characterization and Cloning of the mRNAs Specific for the Lactating Mouse Mammary Gland

Abstract

We have characterized and cloned the lactation-specific mRNAs of mouse mammary glands. The group of eight milk-protein-specific mRNAs were identified (a) by size and antigenic properties of their translation products in vitro and (b) by characterization of their respective cDNA clones. Two x-caseins (43 kDa and 39 kDa) are encoded by mRNAs of 1600 nucleotides and two a-caseins (26 kDa) are encoded by mRNAs of 1450 nucleotides in length. Three smaller caseins, y-casein (23.7 kDa), &casein (21 kDa) and &-casein (14.5 kDa) are synthesized by mRNAs of 880, 1150 and 860 nucleotides. Beside these casein mRNAs a mammary specific 620 nucleotide mRNA codes for a novel acidic whey protein (13.7 kDa).cDNA clones corresponding to the mRNAs for the lactation-specific proteins have been isolated from a mammary-specific cDNA library. Cloned a-casein cDNA hybridizes to both cc-casein specific mRNAs and cloned a-casein cDNAs hybridize with both a-casein specific mRNAs. By RNA blot analysis we show that the cloned cDNAs for mouse a-casein, [)-casein, y-casein and &-casein and the acidic whey protein cross-hybridize with mRNAs of the rat, demonstrating partial sequence homology between the corresponding mRNAs of those species.

Stat5a is mandatory for adult mammary gland development and lactogenesis.

“…Translation of milk protein RNAs results in protein precursors containing signal peptides (Hennighausen and Sippel 1982b). As part of the secretion process these signal peptides are cleaved as the nascent protein chain is translocated into the endoplasmic reticulum.…”

“…Although the genes in question are still elusive, the WAP gene may be a promising candidate. WAP is a mammary protein belonging to a family of protease inhibitors containing a four-disulfide core, but its role in normal mammary function is unknown (Hennighausen and Sippel 1982a). Its expression during pregnancy is tightly regulated, and precocious activation in transgenic mice also results in a developmental arrest at mid-pregnancy, small lumina, and a milchlos phenotype (Burdon et al 1991b).…”

Introduction: Hormonal Regulation of Mammary Development and Milk Protein Gene Expression at the Whole Animal and Molecular Levels

“…The most important early article (1975) on this subject, reproduced here, was written by Jeffrey Rosen of Baylor College of Medicine, who continues as a leader in this field to this day. This article and the many that followed [15,16] ushered in the molecular era in our understanding of the regulation of milk secretion. For an entrée into the current literature on this subject the reader is referred to several timely reviews in this journal [17][18][19][20][21][22][23] as well as key current articles [24][25][26][27].…”

Growth Control and Differentiation in Mammary Epithelial Cells

“…The more recent approach is focused on studying transcription and stability and accumulation of specific messenger RNAs for milk proteins; cDNAs are available for some of the known caseins, a-lactalbumin, and whey acidic protein (61)(62)(63)(64)(65).…”