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ROBO1 is required for postnatal growth and survival

Nicole Aurora Kirk, Ye Eun Hwang, Seul Gi Lee, Juyeon Kang and 5 more

Genes & Genomics | Sep 1, 2026

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It is suggested that ROBO1 contributes to the postnatal development and functional maintenance of multiple organs, with associated modulation of the GH/IGF-1 axis, potentially influencing survival.

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Roundabout guidance receptor 1 (ROBO1) is critical for various processes essential to mammalian development. However, its role in postnatal development and growth remains poorly understood, primarily due to perinatal lethality in knockout models. Robo1 knockout mice on a mixed B6/129S genetic background survive into adulthood and exhibit previously unreported abnormalities across multiple organs. These mice display stunted growth and organ-specific defects, including enlarged lung alveoli, premature hair graying, and diminished subcutaneous fat. Notably, these mice have a reduced lifespan. At 23 days of age, corresponding to the beginning of early puberty in mice, Robo1 knockout mice show significantly reduced plasma levels of growth hormone (GH) and insulin-like growth factor 1 (IGF-1), paralleling decreased expression in the pituitary gland and liver, respectively, compared to wild-type littermates. These findings suggest that ROBO1 contributes to the postnatal development and functional maintenance of multiple organs, with associated modulation of the GH/IGF-1 axis, potentially influencing survival. Further studies with larger cohorts are warranted to elucidate the broader implications of ROBO1 deficiency, particularly in relation to human developmental disorders such as growth hormone deficiencies.

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Nicole Aurora Kirk

first | University of Virginia

Ye Eun Hwang

middle | University of Virginia

Seul Gi Lee

middle | University of Virginia | ORCID 0000-0001-8186-0886

Juyeon Kang

middle | University of Virginia

Kate-Lin Ly

middle | University of Virginia

Yong Yu Gan

middle | University of Virginia

Sangmyung Rhee

middle | Chung-Ang University | ORCID 0000-0003-2733-2147

Kee‐Beom Kim

middle | Kyungpook National University | ORCID 0000-0003-0132-8924

Kwon-Sik Park

last | University of Virginia | ORCID 0000-0003-3346-9086

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BibTeX

@article{Kirk2026ROBO1,
  title = {ROBO1 is required for postnatal growth and survival},
  author = {Nicole Aurora Kirk and Ye Eun Hwang and Seul Gi Lee and Juyeon Kang and Kate-Lin Ly and Yong Yu Gan and Sangmyung Rhee and Kee‐Beom Kim and Kwon-Sik Park},
  journal = {Genes & Genomics},
  year = {2026},
  doi = {10.1007/s13258-026-01802-7},
  url = {https://doi.org/10.1007/s13258-026-01802-7}
}

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