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Previous Ikzf1 mouse models have demonstrated the dual role for IKZF1 in both B and T cell development and have indicated differential requirements of each zinc finger. Furthermore, mutations in IKZF1 are known to cause common variable immunodeficiency in patients characterized by a loss of B cells and reduced Ab production. Through N-ethyl-N-nitrosourea mutagenesis, we have discovered a novel Ikzf1 mutant mouse with a missense mutation (L132P) in zinc finger 1 (ZF1) located in the DNA binding domain. Unlike other previously reported murine Ikzf1 mutations, this L132P point mutation (Ikzf1L132P) conserves overall protein expression and has a B cell\u2013specific phenotype with no effect on T cell development, indicating that ZF1 is not required for T cells. Mice have reduced Ab responses to immunization and show a progressive loss of serum Igs compared with wild-type littermates. IKZF1L132P overexpressed in NIH3T3 or HEK293T cells failed to localize to pericentromeric heterochromatin and bind target DNA sequences. Coexpression of wild-type and mutant IKZF1, however, allows for localization to pericentromeric heterochromatin and binding to DNA indicating a haploinsufficient mechanism of action for IKZF1L132P. Furthermore, Ikzf1+\/L132P mice have late onset defective Ig production, similar to what is observed in common variable immunodeficiency patients. RNA sequencing revealed a total loss of Hsf1 expression in follicular B cells, suggesting a possible functional link for the humoral immune response defects observed in Ikzf1L132P\/L132P mice.<\/jats:p>","DOI":"10.4049\/jimmunol.1901464","type":"journal-article","created":{"date-parts":[[2021,3,3]],"date-time":"2021-03-03T17:16:23Z","timestamp":1614791783000},"page":"1505-1514","source":"Crossref","is-referenced-by-count":4,"title":["A Point Mutation in IKAROS ZF1 Causes a B Cell Deficiency in Mice"],"prefix":"10.1093","volume":"206","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0089-7551","authenticated-orcid":false,"given":"Brigette","family":"Boast","sequence":"first","affiliation":[{"name":"Department of Immunology and Infectious Disease, John Curtin School of Medical Research, The Australian National University , Canberra, Australian Capital Territory 2601 ,","place":["Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lisa A","family":"Miosge","sequence":"additional","affiliation":[{"name":"Department of Immunology and Infectious Disease, John Curtin School of Medical Research, The Australian National University , Canberra, Australian Capital Territory 2601 ,","place":["Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hye Sun","family":"Kuehn","sequence":"additional","affiliation":[{"name":"Immunology Service, Department of Laboratory Medicine, National Institutes of Health Clinical Center , Bethesda, MD 20892"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9039-9876","authenticated-orcid":false,"given":"Vicky","family":"Cho","sequence":"additional","affiliation":[{"name":"Department of Immunology and Infectious Disease, John Curtin School of Medical Research, The Australian National University , Canberra, Australian Capital Territory 2601 ,","place":["Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5764-5948","authenticated-orcid":false,"given":"Vicki","family":"Athanasopoulos","sequence":"additional","affiliation":[{"name":"Department of Immunology and Infectious Disease, John Curtin School of Medical Research, The Australian National University , Canberra, Australian Capital Territory 2601 ,","place":["Australia"]},{"name":"Centre for Personalised Immunology, John Curtin School of Medical Research, The Australian National University , Canberra, Australian Capital Territory 2601 ,","place":["Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6347-6215","authenticated-orcid":false,"given":"Hayley A","family":"McNamara","sequence":"additional","affiliation":[{"name":"Department of Immunology and Infectious Disease, John Curtin School of Medical Research, The Australian National University , Canberra, Australian Capital Territory 2601 ,","place":["Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9553-5304","authenticated-orcid":false,"given":"Yovina","family":"Sontani","sequence":"additional","affiliation":[{"name":"Department of Immunology and Infectious Disease, John Curtin School of Medical Research, The Australian National University , Canberra, Australian Capital Territory 2601 ,","place":["Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan","family":"Mei","sequence":"additional","affiliation":[{"name":"Department of Immunology and Infectious Disease, John Curtin School of Medical Research, The Australian National University , Canberra, Australian Capital Territory 2601 ,","place":["Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Debbie","family":"Howard","sequence":"additional","affiliation":[{"name":"Department of Immunology and Infectious Disease, John Curtin School of Medical Research, The Australian National University , Canberra, Australian Capital Territory 2601 ,","place":["Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6472-7116","authenticated-orcid":false,"given":"Henry J","family":"Sutton","sequence":"additional","affiliation":[{"name":"Department of Immunology and Infectious Disease, John Curtin School of Medical Research, The Australian National University , Canberra, Australian Capital Territory 2601 ,","place":["Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sofia A","family":"Omari","sequence":"additional","affiliation":[{"name":"Department of Immunology and Infectious Disease, John Curtin School of Medical Research, The Australian National University , Canberra, Australian Capital Territory 2601 ,","place":["Australia"]},{"name":"Children's Cancer Institute, School of Women's and Children's Health, Lowy Cancer Centre, University of New South Wales , Sydney, New South Wales 2031 ,","place":["Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4763-4698","authenticated-orcid":false,"given":"Zhijia","family":"Yu","sequence":"additional","affiliation":[{"name":"Department of Immunology and Infectious Disease, John Curtin School of Medical Research, The Australian National University , Canberra, Australian Capital Territory 2601 ,","place":["Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9111-9717","authenticated-orcid":false,"given":"Mariam","family":"Nasreen","sequence":"additional","affiliation":[{"name":"Australian Phenomics Facility, John Curtin School of Medical Research, The Australian National University , Canberra, Australian Capital Territory 2601 ,","place":["Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"T Daniel","family":"Andrews","sequence":"additional","affiliation":[{"name":"Department of Immunology and Infectious Disease, John Curtin School of Medical Research, The Australian National University , Canberra, Australian Capital Territory 2601 ,","place":["Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8220-9294","authenticated-orcid":false,"given":"Ian A","family":"Cockburn","sequence":"additional","affiliation":[{"name":"Department of Immunology and Infectious Disease, John Curtin School of Medical Research, The Australian National University , Canberra, Australian Capital Territory 2601 ,","place":["Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5296-6155","authenticated-orcid":false,"given":"Christopher C","family":"Goodnow","sequence":"additional","affiliation":[{"name":"Immunology Division, Garvan Institute of Medical Research , Darlinghurst, New South Wales 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