MOUSE MUTANTS AS MODELS IN ENDOCRINE RESEARCH

¹ Department of Human Anatomy, South Parks Road, Oxford OX1 3QX

Although Shire (1979) has listed some forty-eight mouse mutants of interest to the endocrinologist, this short review has concentrated upon eleven mutations which have resulted in a significant number of scientific publications over the last 4 or 5 years. The selection of references has had to be limited, but it should be possible easily to expand the list given in this review.

Although the proximate cause of none of the eleven mutations has been identified with certainty, the abnormalities of function have included hormone deficiencies and receptor and post-receptor malfunctions.

It is perhaps a reflexion on our society in the 1980s, that the bulk of research has concentrated on the obese mouse. However, we still do not know the initial cause of this syndrome.

The major disadvantage of the mouse to the hormone assayist lies in the small blood volume and the extreme difficulty in taking serial blood samples over a short period of time. With increased sophistication of assay techniques this may prove less daunting, but is an area where a review of the literature reveals discrepancies between laboratories, and even between data generated by the same laboratory at different times. With regard to the hormone content of endocrine tissues, the way forward for peptide-secreting glands may be in the measurement of mRNA levels for particular hormones. Certainly the methods of recombinant-DNA technology will yield positive information upon the aetiology and expression of some of the syndromes considered above.

Organ transplantation is an area in which mutant mice have proved useful, for example gonadal, pituitary and pancreatic tissue transplantation. The grafting of neural tissue in the hpg mouse has added a further dimension to this field of research.

The great infrastructure of genetical research in mice has enabled us to breed mutant genes onto different genetic backgrounds. This area of research is one which deserves to expand. The techniues of in vitro fertilization, chimera formation and embryo transfer have been used, in part, in studies on mouse mutants, and should provide technical means for further investigating gene expression.

The family of dwarf mutants are ideally suited for research into the expression of genes micro-injected into the fertilized egg (see Charlton & Cox, 1983).

As new hormones are isolated and become available for study these mouse mutants may well be useful in delineating physiological functions for natural and pharmacological products. Again, the dwarf mutants would seem ideally suited for research into the synthesis and action of GRF.

Mouse mutants have proved of use to biochemists and embryologists and provide fertile ground for endocrine investigations ranging from molecular genetics to membrane biophysics.

This article has been cited by other articles:

				M. L. Piper, E. K. Unger, M. G. Myers Jr., and A. W. Xu Specific Physiological Roles for Signal Transducer and Activator of Transcription 3 in Leptin Receptor-Expressing Neurons Mol. Endocrinol., March 1, 2008; 22(3): 751 - 759. [Abstract] [Full Text] [PDF]

				M. Barbieri, M. Bonafe, C. Franceschi, and G. Paolisso Insulin/IGF-I-signaling pathway: an evolutionarily conserved mechanism of longevity from yeast to humans Am J Physiol Endocrinol Metab, November 1, 2003; 285(5): E1064 - E1071. [Abstract] [Full Text] [PDF]

				A. P. N. Themmen and I. T. Huhtaniemi Mutations of Gonadotropins and Gonadotropin Receptors: Elucidating the Physiology and Pathophysiology of Pituitary-Gonadal Function Endocr. Rev., October 1, 2000; 21(5): 551 - 583. [Abstract] [Full Text]