ArticleProceedings of the National Academy of Sciences of the United States of America2010
Homozygous DNA ligase IV R278H mutation in mice leads to leaky SCID and represents a model for human LIG4 syndrome.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
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Who cites it
29 citing papers in PubMed, 48 citations in OpenAlex.
- LIG4 Syndrome Presenting with Extensive Cutaneous Viral Warts Caused by Multi-Type HPV Infection.Genes · 2026Article
- Ku70-SAP domain has an overlapping function with DNA-PKcs in limiting the lateral movement of the Ku ring along DNA.Nucleic acids research · 2026Article
- Preimplantation genetic testing for four families with severe combined immunodeficiency: Three unaffected livebirths.Orphanet journal of rare diseases · 2025Article
- Case Report: Hypomorphic Ligase 4 deficiency - a paradigm of immunodysregulation.Frontiers in immunology · 2025Article
- Autoimmunity and immunodeficiency associated with monoallelic LIG4 mutations via haploinsufficiency.The Journal of allergy and clinical immunology · 2023Article
- Phosphorylation of DNA-PKcs at the S2056 cluster ensures efficient and productive lymphocyte development in XLF-deficient mice.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- Epigenetic reversal of hematopoietic stem cell aging in Phf6-knockout mice.Nature aging · 2022Article
- Case Report: Wide Spectrum of Manifestations of Ligase IV Deficiency: Report of 3 Cases.Frontiers in immunology · 2022Article
- Characterization of a Cohort of Patients With LIG4 Deficiency Reveals the Founder Effect of p.R278L, Unique to the Chinese Population.Frontiers in immunology · 2021Article
- Article
- The recent advances in non-homologous end-joining through the lens of lymphocyte development.DNA repair · 2020Review
- Ligase IV syndrome can present with microcephaly and radial ray anomalies similar to Fanconi anaemia plus fatal kidney malformations.European journal of medical genetics · 2020Article
- Spatiotemporal Gradient of Cortical Neuron Death Contributes to Microcephaly in Knock-In Mouse Model of Ligase 4 Syndrome.The American journal of pathology · 2019Article
- Kinase-dependent structural role of DNA-PKcs during immunoglobulin class switch recombination.Proceedings of the National Academy of Sciences of the United States of America · 2018Article
- DNA ligase IV syndrome; a review.Orphanet journal of rare diseases · 2016Review
- Ligase-4 Deficiency Causes Distinctive Immune Abnormalities in Asymptomatic Individuals.Journal of clinical immunology · 2016Article
- The DNA Ligase IV Syndrome R278H Mutation Impairs B Lymphopoiesis via Error-Prone Nonhomologous End-Joining.Journal of immunology (Baltimore, Md. : 1950) · 2016Article
- A patient with polymerase E1 deficiency (POLE1): clinical features and overlap with DNA breakage/instability syndromes.BMC medical genetics · 2015Article
- Modeling the study of DNA damage responses in mice.Methods in molecular biology (Clifton, N.J.) · 2015Review
- Extreme growth failure is a common presentation of ligase IV deficiency.Human mutation · 2014Article
Corrections and comments
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Authors and funding
22 authors at 4 institutions in 2 countries.
Funding
Abstract
DNA ligase IV (LIG4) is an essential component of the nonhomologous end-joining (NHEJ) repair pathway and plays a key role in V(D)J recombination. Hypomorphic LIG4 mutations in humans are associated with increased cellular radiosensitivity, microcephaly, facial dysmorphisms, growth retardation, developmental delay, and a variable degree of immunodeficiency. We have generated a knock-in mouse model with a homozygous Lig4 R278H mutation that corresponds to the first LIG4 mutation reported in humans. The phenotype of homozygous mutant mice Lig4(R278H/R278H) (Lig4(R/R)) includes growth retardation, a decreased life span, a severe cellular sensitivity to ionizing radiation, and a very severe, but incomplete block in T and B cell development. Peripheral T lymphocytes show an activated and anergic phenotype, reduced viability, and a restricted repertoire, reminiscent of human leaky SCID. Genomic instability is associated with a high rate of thymic tumor development. Finally, Lig4(R/R) mice spontaneously produce low-affinity antibodies that include autoreactive specificities, but are unable to mount high-affinity antibody responses. These findings highlight the importance of LIG4 in lymphocyte development and function, and in genomic stability maintenance, and provide a model for the complex phenotype of LIG4 syndrome in humans.
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