A missense mutation in LRR8 of RXFP2 is associated with cryptorchidism

Abstract

Using genome-wide mutagenesis with N-ethyl-N-nitrosourea (ENU), a mouse mutant with cryptorchidism was identified. Genome mapping and exon sequencing identified a novel missense mutation (D294G) in Relaxin/insulin-like family peptide receptor 2 (Rxfp2). The mutation impaired testicular descent and resulted in decreased testis weight in Rxfp2 DG/DG mice compared to Rxfp2 +/DG and Rxfp2 +/+ mice. Testicular histology of the Rxfp2 DG/DG mice revealed spermatogenic defects ranging from germ cell loss to tubules with Sertoli-cell-only features. Genetic complementation analysis using a loss-of-function allele (Rxfp2 -) confirmed causality of the D294G mutation. Specifically, mice with one of each ..