International Mammalian Genome Society

The 16th International Mouse Genome Conference (2002)

Plenary Presentations * Oral Presentations *
Poster Presentations: Complex Genetics and Disease Modifiers * Developmental Genetics * Functional Genomics * Gene Discovery * Genetic Manipulations to Alter Gene Function * Mouse Models: Human Disease and Pharmacogenetics * Sequence Annotation and Comparative Analysis of Genomes *
Attendees * Sponsors * Table of Contents * Photographs * Awards

Oral Presentation

Tuesday 19 November

09:00 - 09:15 HRS

GENETICS OF TESTICULAR DESCENT AND CRYPTORCHIDISM

A Agoulnik
Baylor College of Medicine

Co-Authors: Bogatcheva N, Kamat A, Gorlov I
Institutions: Baylor College of Medicine

A distinctive manifestation of male dimorphism in many animals is a scrotal position of their gonads. During development the testes descend through a complex, multistage process whereby the embryonic gonads migrate from their initial abdominal position to the scrotum. Recently, we described a mouse transgene insertional mutation, crsp, causing high intra-abdominal cryptorchidism in homozygous males. The integration was accompanied by a 550 kb deletion in the proximal part of chromosome 5, affecting among others, a new gene named Great. The gene encodes a novel G protein-coupled receptor and belongs to the same family of GPCRs as the glycoprotein hormone receptors. We showed that genetic targeting of the Great gene in mice causes bilateral intra-abdominal cryptorchidism. The gubernaculae of the mutant males fail to differentiate, indicating that the Great gene controls their development. Using a variety of molecular and genetic methods we have established that INSL3 hormone is a cognate ligand of the GREAT receptor. We have shown that the expression of GREAT is controlled by SF1 transcription factor.  Furthermore, we have cloned the human GREAT gene and screened genomic DNAs from cryptorchid patients for the mutations within the gene. A unique missense mutation (T222P) in the ectodomain of the GREAT receptor has been identified in one of the patients. The mutant receptor fails to respond to the ligand stimulation, implicating the GREAT gene in the etiology in some cases of cryptorchidism in humans.