Elsevier

Journal of Pediatric Surgery

Volume 38, Issue 12, December 2003, Pages 1793-1798
Journal of Pediatric Surgery

Transabdominal testicular descent is disrupted in mice with deletion of insulinlike factor 3 receptor

Presented at the 36th Annual Meeting of the Pacific Association of Pediatric Surgeons, Sydney, Australia, May 12–16, 2003.
https://doi.org/10.1016/j.jpedsurg.2003.08.047Get rights and content

Abstract

Background: Several factors are implicated in transabdominal testicular descent, including insulinlike factor 3 (INSL3) hormone and Müllerian-inhibiting substance (MIS). A transgene insertional mutation found on chromosome 5 in the mouse, known as crsp, causes deletion of a transmembrane G protein-coupled receptor gene, Great, which is highly expressed in the gubernaculum. The authors describe here a detailed analysis of the testicular descent and gubernacular development in crsp mice to determine the role of the Great gene in this process.

Methods: Homozygous (crsp/crsp) mutant and wild-type heterozygous (crsp/+) mice were examined at birth (D 0) and at days 10 (D 10) and 30 (D 30) postnatally. Serial sagittal or coronal sections were analyzed for position of the gonads and cremaster sac development.

Results: Transabdominal testicular descent was absent at D 0 in crsp/crsp homozygous mice with no swelling reaction in the gubernacula. By D 10 the cremaster sac was significantly thinner (P < .05) and contained less collagen in the mutants than in the wild-type controls. On D 30 the cremaster sacs of mutant males were similar in thickness to those in females.

Conclusions: Disruption of the Great gene causes failure of the transabdominal phase of descent, identical to that seen in the Insl3-deficient mutants, consistent with the recent data suggesting that Great gene encodes the Insl3 transmembrane receptor. No differences between D 30 mutant males and females were found in the gubernacula, suggesting that Insl3/Great signaling regulates gubernacular development.

Section snippets

Materials and methods

The mutant crsp mice used in this study were produced by intercrossing of heterozygous males and homozygous females. Macroscopically, crsp/+ heterozygous males have the same degree of descent as that in wild-type males; therefore, we have used heterozygous littermates as the wild-type controls.

In this study, 4 crsp/crsp homozygous and 7 heterozygous males at birth (D 0), 5 crsp/crsp homozygous and 5 heterozygous males at day 10 after birth (D 10), and 6 crsp/crsp homozygous males and 5 crsp/crsp

Results

Morphologic analysis of the crsp mutant mice showed inhibition of testicular descent. Mutant testes were located in a high intraabdominal position in all 3 analyzed age groups (Table 1).

Discussion

The results of this study show that the crsp mutation causes an anomaly of transabdominal testicular descent. The homozygote mutant mice had testes high on the posterior abdominal wall adjacent to the kidneys. Molecular genetic analysis of the crsp mutation showed that it caused a deletion of the Great gene encoding a novel G protein-coupled receptor.10 Great is highly expressed in the gubernaculum, testis, brain, and, to a lesser degree, in some other organs. Genetic targeting of the Great

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