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Updated: Dec 20, 2025

In Vivo Modeling of the Morbid Human Genome using Danio rerio
Published on: August 24, 2013
Development and characterization of an Otp conditional loss of function allele
Yu Hu1, Jiamin Li1,2, Yuyuan Zhu1,3
1Shenzhen Key Laboratory for Molecular Biology of Neural Development, Guangdong Provincial Key Laboratory of Brain Connectome and Behavior, CAS Key Laboratory of Brain Connectome and Manipulation, The Brain Cognition and Brain Disease Institute, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences; Shenzhen-Hong Kong Institute of Brain Science, Shenzhen, China.
Abstract:
Orthopedia (Otp) is a homeodomain transcription factor that plays an essential role in the development of hypothalamic neurosecretory systems. Loss of Otp results in the failure of differentiation of key hypothalamic neuroendocrine cell types, and pups die soon after birth. Although the constitutive knockout Otp mouse model (Otp KO ) has significantly expanded our understanding of Otp's function in vivo, a conditional loss of function Otp allele that enables tissue or cell-type specific ablation of Otp has not been developed. Here, we used CRISPR/Cas9 gene-editing technology to generate a conditional Otp knockout mouse line in which exon 2 of the murine Otp gene is flanked by LoxP sites (Otp f/f ). Crossing the Otp f/f mouse with Agrp-Ires-cre mouse, we demonstrate the requirement for Otp in the continuous differentiation of AgRP neurons after cell fate determination. We also show that the residual AgRP neurons in Agrp-Ires-cre;Otp f/f mice project to similar downstream target regions. This newly developed Otp f/f mouse can be used to explore the functions of Otp with cell-type or temporal specificity.
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