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Abnormal neural crest innervation in Sox10-Venus mice with all-trans retinoic acid-induced anorectal malformations

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Abstract

Background/purpose

Despite technical advances in the surgical/medical care of anorectal malformation (ARM), persistent unsatisfactory postoperative bowel habit has been attributed to histopathologic abnormalities of the distal rectum/pouch (DRP) and hypoplasia of anal sphincter muscles (ASM). We used Sox10-Venus mice with ARM induced by all-trans retinoic acid (ATRA) to investigate neural crest cell (NCC) innervation in the DRP and ASM.

Method

Pregnant Sox10-Venus mice were administered single doses of 50, 70, or 100 mg/kg of ATRA on embryonic day 8.5 (E8.5) then sacrificed on either E16.5 or E19.5. Bowel specimens comprising the anorectum were examined using fluorescence microscopy without immunohistochemical staining (FMIS). Anti-PGP9.5 was used to delineate ganglion cells and anti-SMA for smooth muscles.

Results

The appropriate dose of ATRA for inducing ARM was 50 mg/kg. Under FMIS, all ARM embryos (n = 5; all high type; 3 male:2 female) had less NCC innervation with thick Venus-positive nerve fibers in the DRP compared with normal embryos (n = 8); there was abnormal NCC innervation in the DRP and absent ASM in ARM mice.

Conclusion

We are the first to delineate abnormal enteric nervous system innervation in the DRP of ARM mice without using immunohistochemical staining techniques thus allowing specimens to be examined without any distortion.

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Acknowledgments

We are very grateful for technical support from the Division of Biomedical Imaging Research, BioMedical Research Center, Juntendo Graduate School of Medicine. This work was supported by the Ministry of Health, Welfare, and Labour, Japan, and the Ministry of Education, Culture, Sports, Science and Technology, Japan.

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Authors and Affiliations

  1. Department of Biochemistry and Biophysics, Graduate School of Health Care Sciences, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, 113-8510, Tokyo, Japan

    Ryota Suzuki, Yo Mabuchi, Nobuharu Suzuki & Chihiro Akazawa

  2. Department of Pediatric General and Urogenital Surgery, Juntendo University School of Medicine, 113-8421, Tokyo, Japan

    Katsumi Miyahara, Hiroshi Murakami, Takashi Doi, Geoffrey J. Lane & Atsuyuki Yamataka

Authors
  1. Ryota Suzuki
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  2. Katsumi Miyahara
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  3. Hiroshi Murakami
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  4. Takashi Doi
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  5. Geoffrey J. Lane
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  6. Yo Mabuchi
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  7. Nobuharu Suzuki
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  8. Atsuyuki Yamataka
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  9. Chihiro Akazawa
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Correspondence to Chihiro Akazawa.

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Suzuki, R., Miyahara, K., Murakami, H. et al. Abnormal neural crest innervation in Sox10-Venus mice with all-trans retinoic acid-induced anorectal malformations. Pediatr Surg Int 30, 189–195 (2014). https://doi.org/10.1007/s00383-013-3452-z

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  • DOI: https://doi.org/10.1007/s00383-013-3452-z

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