AJP - Regulatory, Integrative and Comparative Physiology, Vol 264, Issue 1 12-R15, Copyright © 1993 by American Physiological Society
The Zucker fatty (fa) gene is not a mutation of corticotropin-releasing factor
J. W. Smoller, G. E. Truett, J. Hirsch and R. L. Leibel
Laboratory of Human Behavior and Metabolism, Rockefeller University, New York, New York 10021.
Corticotropin-releasing factor (CRF) appears to regulate several
physiological systems that display prominent abnormalities in Zucker fatty
(fa/fa) rats, including the hypothalamic-pituitary-adrenal axis, the
autonomic nervous system, and feeding behavior. Moreover, central
administration of CRF ameliorates the obese phenotype. In light of these
observations, the gene for CRF is a plausible candidate for the defective
gene in the Zucker fatty rat. We report here the use of molecular genetic
linkage analysis to test the hypothesis that fa is a mutant allele of the
CRF gene. A restriction fragment length polymorphism for CRF between Zucker
(13M) and Brown Norway (BN) DNA allowed us to examine segregation of 13M
and BN CRF alleles relative to fa in 58 obese (fa/fa) F2 progeny of a 13MBN
fa/+F1 intercross. If fa = CRF, all animals homozygous for the fatty
mutation should be homozygous for the 13M CRF allele. However, only 10/58
fa/fa animals were homozygous for the 13M CRF allele, indicating that fa
and CRF are not allelic. Thus, although CRF may be important in the
physiology of Zucker rat obesity, fa is not a CRF mutation. Using a mouse
C57BL/6J Spretus F1 x C57BL DBA/2J F1 intercross, we were able to
demonstrate that the mouse CRF gene is linked to the carbonic anhydrase II
(Car-2) gene on mouse chromosome 3, in a region of synteny-homology with
rat chromosome 2. Thus the rat CRF gene is probably located on chromosome
2.
