Why Are Scottie Dogs So Small and Great Danes So Big?

There is an interesting piece in the New York Times today ( Friday April 6, 2007, page A13) entitled “Difference Between Mutts and Jeffs? A Gene,” written by Donald G. McNeil, Jr. Before I get to the article, I need to tell you something about how children grow. There are many genetic and environmental factors that influence rate of growth and ultimate adult stature (just like there are many genetic and environmental factors that contribute to body weight).

For the moment, let’s just focus on some known hormonal influences on growth. Hormones are substances, usually polypeptides or proteins, that send messages to cells telling them what to do. We know that a hormone called growth hormone-releasing hormone (GHRH) which is produced in the hypothalamus (part of the brain), stimulates the pituitary gland (also in the brain) to produce and secrete another hormone called growth hormone (GH). GH circulates bound to a protein called GH-binding protein GHBP. The GH/GHBP complex binds to the liver where it stimulates production and secretion of another hormone called insulin growth factor 1 (IGF-1). IGF-1 circulates in the blood bound to another protein, IGFBP-3. Finally, the IGF-1/IGFBP-3 complex binds to tissues throughout the body, particularly muscle and bone, to promote growth. Sounds complicated? I suppose, but it’s a pretty slick system. We now know that in complex systems just about everything that could go wrong will. That is true for the growth hormone system; abnormalities and genetic variations have been described for each of the steps leading to the final expression of growth hormone secretion which is growth.

Growth hormone deficiency is one of the known causes for poor linerar growth. There are many different reasons for growth hormone deficiency (e.g., an absent pituitary gland, a pituitary gland damaged by radiation for treatment of a brain tumor, a genetic defect in formation of IGF-1). Thus GH deficiency is really a term used to describe a large number of possible abnormalities in the hormonal chain from the brain GHRH to the binding of the IGF-1/IGFBP3 complex in the tissues targeted for growth.

Back to the news report

So, the news article published today summarizes a study published today in the journal Science. According to the news report, the study which was led by Elaine A. Ostrander from the National Human Genome Research Institute, analyzed more than 3000 purebreds from 143 breeds. The researchers found that virtually all small dog breeds had a tiny bit of DNA that suppressed the “insulin-like growth factor 1” gene; this suppressor gene was not present in large dog breeds. From what we discussed above, you can predict exactly what such a suppressor gene would do to linear growth and why: growth is slowed in the small dog breeds because they can’t generate nearly as much IGF-1 as the large dog breeds. So, in effect, small dog breeds have growth hormone deficiency, partial or complete depending on the extent of the IGF-1 suppression.

What are the clinical implications?

In humans, IGF-1 has been synthesized through recombinant DNA techniques and is being used in certain clinical situations. I’m not certain, but I think IGF-1s are species-specific (as are pituitary growth hormones). If this is true one probably couldn’t make a juvenile Scottie dog into a Great Dane-sized Scottie dog adult by giving human IGF-I injections. But who’s going to stop some enterprising scientist from trying it or from making a variety of small dog IGF-1s? Of course, one could also argue that we should insert the suppressor DNA into the genome of lovable large dogs to make them small and lovable? Oh the possibilites are just endless? Isn’t genetics interesting?

Anyway, in future entries, I promise to come back to growth hormone and growth in children. This news report was just too interesting to ignore.

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