Search Results

You are looking at 1 - 1 of 1 items for

  • Author: Tomoaki Murakami x
  • Refine by access: All content x
Clear All Modify Search
Noboru Uchida Department of Pediatrics, Keio University School of Medicine, Tokyo, Japan

Search for other papers by Noboru Uchida in
Google Scholar
PubMed
Close
,
Tomohiro Ishii Department of Pediatrics, Keio University School of Medicine, Tokyo, Japan

Search for other papers by Tomohiro Ishii in
Google Scholar
PubMed
Close
,
Naoko Amano Department of Pediatrics, Keio University School of Medicine, Tokyo, Japan
Department of Pediatrics, Saitama City Hospital, Saitama, Japan

Search for other papers by Naoko Amano in
Google Scholar
PubMed
Close
,
Shuji Takada Department of Systems BioMedicine, National Research Institute for Child Health and Development, Tokyo, Japan

Search for other papers by Shuji Takada in
Google Scholar
PubMed
Close
,
Kyoko Kobayashi Laboratory of Veterinary Toxicology, Tokyo University of Agriculture and Technology, Tokyo, Japan

Search for other papers by Kyoko Kobayashi in
Google Scholar
PubMed
Close
,
Tomoaki Murakami Laboratory of Veterinary Toxicology, Tokyo University of Agriculture and Technology, Tokyo, Japan

Search for other papers by Tomoaki Murakami in
Google Scholar
PubMed
Close
,
Satoshi Narumi Department of Pediatrics, Keio University School of Medicine, Tokyo, Japan
Department of Molecular Endocrinology, National Research Institute for Child Health and Development, Tokyo, Japan

Search for other papers by Satoshi Narumi in
Google Scholar
PubMed
Close
, and
Tomonobu Hasegawa Department of Pediatrics, Keio University School of Medicine, Tokyo, Japan

Search for other papers by Tomonobu Hasegawa in
Google Scholar
PubMed
Close

Wnt/β-catenin signaling is essential for adrenocortical development. Zinc and ring finger 3 (ZNRF3), an E3 ubiquitin ligase that attenuates Wnt/β-catenin signaling, is negatively regulated by R-spondin via an extracellular domain that is partially encoded by exon 2 of ZNRF3. We recently identified ZNRF3 exon 2 deletions in three individuals with congenital adrenal hypoplasia. ZNRF3 exon 2 deletion impairs R-spondin binding, thereby attenuating β-catenin expression and eventually leading to the development of congenital adrenal hypoplasia. To elucidate the influence of ZNRF3/Znrf3 exon 2 deletion on adrenocortical development, we generated homozygous Znrf3 exon 2 deletion (Znrf3 Δ2/Δ2) mice. Whereas the adrenal glands of Znrf3 Δ2/Δ2 mice did not show gross morphological changes at birth, moderate hyperplasia of the zona fasciculata (ZF), dispersed medulla arrangement, and a radially spreading zone with macrophage infiltration between the ZF and medulla were observed at 6 weeks of age. 20α-hydroxysteroid dehydrogenase, a marker of the adrenal X-zone, was hardly detected by immunostaining, and gene expression was significantly downregulated. The number of activated β-catenin-positive cells decreased in the zona glomerulosa, consistent with the results of in situ hybridization for Axin2, a Wnt/β-catenin target gene. Plasma ACTH and serum corticosterone levels in Znrf3 Δ2/Δ2 mice did not differ significantly from those in wild-type mice. These results show a species-specific difference in the effects of ZNRF3/Znrf3 exon 2 deletions in humans and mice; Znrf3 Δ2/Δ2 mice do not develop congenital adrenal hypoplasia but instead exhibit moderate ZF hyperplasia, dispersed medulla arrangement, X-zone dysplasia, and macrophage infiltration occurred in the inner cortex.

Restricted access