Evidence map›Paper›PMID 40420248›Full record

ArticleOrphanet journal of rare diseases2025

Phenotypic study of humanized mice carrying the PAH deep intronic variant c.1199+502A>T.

Chuan Zhang, Yousheng Yan, Bingbo Zhou, Huimin Gao, Xiaohua Jin, Ling Hui, Shengju Hao, Zongfu Cao, Xu Ma

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Article in Orphanet journal of rare diseases, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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4 · The record

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5 · Who and what money

Authors and funding

9 authors.

Chuan Zhang *Gansu Province Medical Genetics Center, Gansu Provincial Maternity and Child-Care Hospital, Gansu Provincial Central Hospital, Lanzhou, China.
Yousheng Yan *Department of Prenatal Diagnosis, Beijing Obstetrics and Gynecology Hospital, Beijing Maternal and Child Health Care Hospital, Capital Medical University, Beijing, China.
Bingbo Zhou *Gansu Province Medical Genetics Center, Gansu Provincial Maternity and Child-Care Hospital, Gansu Provincial Central Hospital, Lanzhou, China.
Huimin GaoDepartment of Prenatal Diagnosis, Beijing Obstetrics and Gynecology Hospital, Beijing Maternal and Child Health Care Hospital, Capital Medical University, Beijing, China.
Xiaohua JinNational Research Institute for Family Planning, National Human Genetic Resources Center, Beijing, China.
Ling HuiGansu Province Medical Genetics Center, Gansu Provincial Maternity and Child-Care Hospital, Gansu Provincial Central Hospital, Lanzhou, China.
Shengju HaoGansu Province Medical Genetics Center, Gansu Provincial Maternity and Child-Care Hospital, Gansu Provincial Central Hospital, Lanzhou, China.
Zongfu CaoNational Research Institute for Family Planning, National Human Genetic Resources Center, Beijing, China. zongfu_cao@163.com.ORCID http://orcid.org/0000-0002-9707-8765
Xu MaNational Research Institute for Family Planning, National Human Genetic Resources Center, Beijing, China. maxubioinfo@163.com.

Funding

Beijing Natural Science Foundation 7232062Gansu Provincial Clinical Research Center for Birth Defects and Rare Diseases 21JR7RA680Gansu Provincial Science and Technology Plan Funding Project 22YF7FA094National Key Research and Development Program of China 2016YFC1000307National Population and Reproductive Health Science Data Center 2005DKA32408National Science and Technology Resource Sharing Service Platform Project YCZYPT[2020]05-03
6 · The paper itself

Abstract

backgroundThe c.1199 + 502 A > T variant of the phenylalanine hydroxylase (PAH) gene, which is the most frequently reported deep intronic variant involved in phenylketonuria (PKU), is mainly observed in patients with classical or mild PKU. Prior to this study, no mouse models of PKU featuring deep intronic variants of PAH had been reported.

methodsTo phenotypically simulate the pathogenicity of this variant, we used CRISPR/Cas9 genome editing technology and homologous recombination to generate homozygous PKU model mice with a partially humanized Pah gene incorporating human PAH exons 11-12 carrying c.1199 + 502 A > T or wild-type (c.1199 + 502WT) control sequences.

resultsHumanized homozygous Pah c.1199 + 502 A > T mice exhibited a classical PKU phenotype, including a higher serum phenylalanine concentration, yellowing of the fur, and other traits. The homozygous mutant group had poorer spatial learning and spatial memory compared with the wild-type group.

conclusionThis construction of the first humanized mice carrying a deep intronic variant of PAH provides a new animal model for the pathogenesis and treatment of PKU, and may serve as a reference for future research on the pathogenicity of deep intronic variation.

Indexed as

Phenylalanine HydroxylasePhenylketonuriasAnimalsDisease Models, AnimalHumansIntronsMicePhenotypePhenylalanine HydroxylaseCRISPR/Cas9Deep intronic variantHumanized micePhenotypicPhenylketonuria

Identifiers

PMID40420248
PMCPMC12107979

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