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Journal of Histochemistry and Cytochemistry, Vol. 51, 555-565, May 2003, Copyright © 2003, The Histochemical Society, Inc.

ARTICLE

Proteotyping of Mammary Tissue from Transgenic and Gene Knockout Mice with Immunohistochemical Markers: a Tool To Define Developmental Lesions

Jonathan M. Shillingforda, Keiko Miyoshia,b, Gertraud W. Robinsona, Brian Bieriea, Yixue Caoc, Michael Karinc, and Lothar Hennighausena
a Laboratory of Genetics and Physiology, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland
b Department of Biochemistry, School of Dentistry, University of Tokushima, Japan
c Laboratory of Gene Regulation and Signal Transduction, Department of Pharmacology, School of Medicine, University of California, San Diego, La Jolla, California

Correspondence to: Jonathan M. Shillingford, Lab. of Genetics and Physiology, NIDDK, NIH, Bethesda, MD 20892. E-mail: jonshi@helix.nih.gov

Through the use of transgenic and gene knockout mice, several studies have identified specific genes required for the functional development of mammary epithelium. Although histological and milk protein gene analyses can provide useful information regarding functional differentiation, they are limited in their ability to precisely define the molecular lesions. For example, mice that carry a mutation in one of the subunits of the I{kappa}B kinase, IKK{alpha}, cannot lactate despite the presence of histologically normal alveolar compartment and the expression of milk protein genes. To further define and understand such lesions on a molecular level, we sought evidence for proteins that are differentially expressed during mammary gland development with a view to generating a tissue proteotype. Using database screens and immunohistochemical analyses, we have identified three proteins that exhibit distinct profiles. Here, using mouse models as test biological systems, we demonstrate the development and application of mammary tissue proteotyping and its use in the elucidation of specific developmental lesions. We propose that the technique of proteotyping will have wide applications in the analyses of defects in other mouse models.

(J Histochem Cytochem 51:555–565, 2003)

Key Words: proteotyping, mammary, development, immunohistochemistry, markers


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