A missense mutation of the Dhh gene is associated with male pseudohermaphroditic rats showing impaired Leydig cell development

Yasuhiro Kawai, Junko Noguchi, Kouyou Akiyama, Yuriko Takeno, Yasuhiro Fujiwara, Shimpei Kajita, Takehito Tsuji, Kazuhiro Kikuchi, Hiroyuki Kaneko, Tetsuo Kunieda

Research output: Contribution to journalArticlepeer-review

37 Citations (Scopus)


Development of the male gonads is a complex process with interaction of various cells in the gonads including germ, Sertoli, Leydig, and myoid cells. TF is a mutant rat strain showing male pseudohermaphroditism, with agenesis of Leydig cells and androgen deficiency controlled by an autosomal single recessive gene (mp). The mp locus was mapped on the distal region of rat chromosome 7 by linkage analysis, but the gene responsible for the mp mutation has not been identified. In this study, we performed fine linkage mapping and sequence analysis to determine the causative gene of the mp mutation, and performed an immunohistochemical study using a Leydig cell-specific marker to investigate detailed phenotypes of the mutant rats during the testicular development. As a result, we found a missense mutation of the gene encoding Desert hedgehog (Dhh) in the mutant rat, which could result in loss of function of the DHH signaling pathway. Histochemical examination revealed remarkably reduced number of fetal Leydig cells and lack of typical spindle-shaped adult Leydig cell in the mp/mp rats. These phenotypes resembled those of the Dhh-null mice. Additionally, testosterone levels were significantly lower in the mp/mp fetus, indicating androgen deficiency during embryonic development. These results indicate that the mutation of the Dhh gene may be responsible for the pseudohermaphrodite phenotypes of the mutant rat, and that the Dhh gene is probably essential for the development of Leydig cells.

Original languageEnglish
Pages (from-to)217-225
Number of pages9
Issue number2
Publication statusPublished - Feb 2011

ASJC Scopus subject areas

  • Reproductive Medicine
  • Embryology
  • Endocrinology
  • Obstetrics and Gynaecology
  • Cell Biology


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