Expression of the whey acidic protein (Wap) is necessary for adequate nourishment of the offspring but not functional differentiation of mammary epithelial cells.
Whey acidic protein (WAP) is the principal whey protein found in rodent milk, which contains a cysteine-rich motif identified in some protease inhibitors and proteins involved in tissue modeling. The expression of the Wap gene, which is principally restricted to the mammary gland, increases more than 1,000-fold around mid-pregnancy. To determine whether the expression of this major milk protein gene is a prerequisite for functional differentiation of mammary epithelial cells, we generated conventional knockout mice lacking two alleles of the Wap gene. Wap-deficient females gave birth to normal litter sizes and, initially, produced enough milk to sustain the offspring. The histological analysis of postpartum mammary glands from knockout dams does not reveal striking phenotypic abnormalities. This suggests that the expression of the Wap gene is not required for alveolar specification and functional differentiation. In addition, we found that Wap is dispensable as a protease inhibitor to maintain the stability of secretory proteins in the milk. Nevertheless, a significant number of litters thrived poorly on Wap-deficient dams, in particular during the second half of lactation. This observation suggests that Wap may be essential for the adequate nourishment of the growing young, which triple in size within the first 10 days of lactation. Important implications of these findings for the use of Wap as a marker for advanced differentiation of mammary epithelial cells and the biology of pluripotent progenitors are discussed in the final section.
Triplett
Aleata A
AA
Eppley Institute for Research in Cancer and Allied Diseases and the Department of Pathology and Microbiology, University of Nebraska Medical Center, Omaha, Nebraska 68198-6805, USA.
Sakamoto
Kazuhito
K
Matulka
Laurice A
LA
Shen
Liya
L
Smith
Gilbert H
GH
Wagner
Kay-Uwe
KU
D000818:Animals; D000975:Antioxidants / Q000502:physiology; D002454:Cell Differentiation / Q000235:genetics*; D005260:Female; D018390:Gene Targeting; D005978:Glutathione / Q000502:physiology; D008321:Mammary Glands, Animal / Q000166:cytology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008892:Milk / Q000378:metabolism*; D008894:Milk Proteins / Q000096:biosynthesis* / Q000235:genetics* / Q000494:pharmacology; D009747:Nutritional Physiological Phenomena / Q000235:genetics*; D011480:Protease Inhibitors / Q000378:metabolism
D000975:Antioxidants; D008894:Milk Proteins; D011480:Protease Inhibitors; C024471:whey acidic proteins; D005978:Glutathione