Beyond big and small mice: applications of mouse molecular genetics in endocrinology: Transgenic Models in Endocrinology edited by Maria Castro. Kluwer, 2001. EUR 210.00/US$189.00/GB£130.00 (xii+265 pages) ISBN 0 7923 7344 8 Transgenics in Endocrinology edited by Martin M. Matzuk, Chester W. Brown and T. Rajendra Kumar. Humana Press, 2001. US$175.00 (x+485 pages) ISBN 0 896 03764 9

Twenty years ago, the very first transgenic mice captured the attention of scientists and the lay press alike when, thanks to the unregulated expression of the growth hormone transgene, they grew to almost double the size of normal mice. This illustrated profoundly that transgenes randomly integrated in the genome can be expressed and dramatically change the physiology of animals. Then came the targeted modification of endogenous mouse genes, using homologous recombination in embryonic stem cells, opening the door to the creation of recessive models of human disease and more controlled genetic alterations. Over the years, genetically engineered mice have been invaluable for testing endocrine paradigms, establishing gene function, studying cancer and establishing useful cell lines through targeted oncogenesis [1]. The applications of gene tailoring are now limited only by our imaginations. Methods are established for avoiding the tedious search for cis-acting regulatory sequences, producing tissue-specific and temporally regulated expression, generation of subtle changes, such as missense mutations, humanizing the mouse genome, and tagging rare cell types with fluorescent markers for cell sorting [2–4]. Presently, the generation and analysis of genetically engineered animals is a compelling approach that is feasible for all scientists, but given that these technologies have been in use for many years, newcomers might be daunted by the task of assimilating the vast literature relevant to their area of endocrinology. Two books, Transgenics in Endocrinology (TIE) and Transgenic Models in Endocrinology (TMIE), summarize the advances made using genetically engineered mice. TIE is more comprehensive, with nearly twice as many chapters as TMIE, and is generally more reference oriented, as most chapters have organized vast amounts of information in accessible tabular format. The strength of TMIE is in the chapters that are reflective and future oriented, including the promise of viral vectors for altering gene expression and the utility of transgenic rats. TIE is part of the Contemporary Endocrinology series, and begins with a thorough introduction to genetic engineering. This brings the novice up to speed on the current technologies of transgenic and knockout mice. A review of sexual differentiation is followed by a review of Mullerian inhibiting substance and, in general, there is considerable emphasis on reproductive endocrinology. Aspects of ovarian and testicular function are covered with complete lists of transgenic mice that have defects in germ cell formation, migration, differentiation and response to exogenous stimuli. The regulation of cell survival in reproductive tissues is addressed. Deregulated cell proliferation in the prostate and other endocrine tissues is achieved with transgenic mice that use tissuespecific promoters to drive expression of immortalizing oncogenes. These mice are used for understanding the consequences of excess proliferation as well as for establishing cell lines representative of various developmental stages [5]. Another important aspect of endocrinology reviewed in TIE is regulation of growth and metabolism. Bartke and co-workers catalog the important transgenic studies on central signaling pathways, growth hormone, insulin and the insulin growth factors. Both books contain in-depth discussions of the expression and function of pituitary hormones. Keri and Nilson, for example, contribute chapters on gonadotropins focused on their contributions to ovarian cancer susceptibility and defects in the genes themselves. Detailed and informative chapters on corticotrophins and pro-opiomelanocortin (POMC) are presented in both books. Low and colleagues present reviews on POMC that are less distinctive from one another, but still unique in their focus and coverage. The cis elements for hormonal regulation of POMC expression, pituitary tumors, POMC toxigenes, and POMC mutations are the focus of TIE, whereas TMIE is unique in its coverage of peptide processing and various POMC-derived peptide receptor genes. Several techniques are covered in TMIE, including the use of viral vectors for delivering genes to endocrine tissue. Also, the use of cell-type specific and inducible transgenes, with emphasis on their use in the anterior pituitary is discussed. Finally, the usefulness of transgenic rats is presented with suggestions for the design of dominant negative and antisense transgenes to circumvent the lack of gene targeting in rats. The use of transgenic rats is Corresponding author: L.T. Raetzman (raetzman@umich.edu). Update TRENDS in Endocrinology and Metabolism Vol.14 No.5 July 2003 204