Abstract
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 language | English |
|---|---|
| Pages (from-to) | 217-225 |
| Number of pages | 9 |
| Journal | Reproduction |
| Volume | 141 |
| Issue number | 2 |
| DOIs | |
| Publication status | Published - Feb 2011 |
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ASJC Scopus subject areas
- Obstetrics and Gynaecology
- Reproductive Medicine
- Embryology
- Endocrinology
- Cell Biology
Cite this
A missense mutation of the Dhh gene is associated with male pseudohermaphroditic rats showing impaired Leydig cell development. / Kawai, Yasuhiro; Noguchi, Junko; Akiyama, Kouyou; Takeno, Yuriko; Fujiwara, Yasuhiro; Kajita, Shimpei; Tsuji, Takehito; Kikuchi, Kazuhiro; Kaneko, Hiroyuki; Kunieda, Tetsuo.
In: Reproduction, Vol. 141, No. 2, 02.2011, p. 217-225.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - A missense mutation of the Dhh gene is associated with male pseudohermaphroditic rats showing impaired Leydig cell development
AU - Kawai, Yasuhiro
AU - Noguchi, Junko
AU - Akiyama, Kouyou
AU - Takeno, Yuriko
AU - Fujiwara, Yasuhiro
AU - Kajita, Shimpei
AU - Tsuji, Takehito
AU - Kikuchi, Kazuhiro
AU - Kaneko, Hiroyuki
AU - Kunieda, Tetsuo
PY - 2011/2
Y1 - 2011/2
N2 - 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.
AB - 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.
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U2 - 10.1530/REP-10-0006
DO - 10.1530/REP-10-0006
M3 - Article
VL - 141
SP - 217
EP - 225
JO - Reproduction
JF - Reproduction
SN - 1470-1626
IS - 2
ER -