{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,23]],"date-time":"2026-06-23T13:13:41Z","timestamp":1782220421664,"version":"3.54.5"},"reference-count":22,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2022,8,17]],"date-time":"2022-08-17T00:00:00Z","timestamp":1660694400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"Foundation Fighting Blindness, Research to Prevent Blindness","doi-asserted-by":"publisher","award":["NIH-RO1EY21237"],"award-info":[{"award-number":["NIH-RO1EY21237"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"Foundation Fighting Blindness, Research to Prevent Blindness","doi-asserted-by":"publisher","award":["RO1EY030591"],"award-info":[{"award-number":["RO1EY030591"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"Foundation Fighting Blindness, Research to Prevent Blindness","doi-asserted-by":"publisher","award":["RO1EY031663"],"award-info":[{"award-number":["RO1EY031663"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"Foundation Fighting Blindness, Research to Prevent Blindness","doi-asserted-by":"publisher","award":["T32EY026590"],"award-info":[{"award-number":["T32EY026590"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"Foundation Fighting Blindness, Research to Prevent Blindness","doi-asserted-by":"publisher","award":["P30-EY22589"],"award-info":[{"award-number":["P30-EY22589"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"Foundation Fighting Blindness, Research to Prevent Blindness","doi-asserted-by":"publisher","award":["R01EY016323"],"award-info":[{"award-number":["R01EY016323"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"Foundation Fighting Blindness, Research to Prevent Blindness","doi-asserted-by":"publisher","award":["2P30CA023100"],"award-info":[{"award-number":["2P30CA023100"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes"],"abstract":"<jats:p>We previously identified a homozygous G178R mutation in human ASRGL1 (hASRGL1) through whole-exome analysis responsible for early onset retinal degeneration (RD) in patients with cone\u2013rod dystrophy. The mutant G178R ASRGL1 expressed in Cos-7 cells showed altered localization, while the mutant ASRGL1 in E. coli lacked the autocatalytic activity needed to generate the active protein. To evaluate the effect of impaired ASRGL1 function on the retina in vivo, we generated a mouse model with c.578_579insAGAAA (NM_001083926.2) mutation (Asrgl1mut\/mut) through the CRISPR\/Cas9 methodology. The expression of ASGRL1 and its asparaginase activity were undetectable in the retina of Asrgl1mut\/mut mice. The ophthalmic evaluation of Asrgl1mut\/mut mice showed a significant and progressive decrease in scotopic electroretinographic (ERG) response observed at an early age of 3 months followed by a decrease in photopic response around 5 months compared with age-matched wildtype mice. Immunostaining and RT-PCR analyses with rod and cone cell markers revealed a loss of cone outer segments and a significant decrease in the expression of Rhodopsin, Opn1sw, and Opn1mw at 3 months in Asrgl1mut\/mut mice compared with age-matched wildtype mice. Importantly, the retinal phenotype of Asrgl1mut\/mut mice is consistent with the phenotype observed in patients harboring the G178R mutation in ASRGL1 confirming a critical role of ASRGL1 in the retina and the contribution of ASRGL1 mutations in retinal degeneration.<\/jats:p>","DOI":"10.3390\/genes13081461","type":"journal-article","created":{"date-parts":[[2022,8,17]],"date-time":"2022-08-17T03:15:27Z","timestamp":1660706127000},"page":"1461","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["A Mouse Model with Ablated Asparaginase and Isoaspartyl Peptidase 1 (Asrgl1) Develops Early Onset Retinal Degeneration (RD) Recapitulating the Human Phenotype"],"prefix":"10.3390","volume":"13","author":[{"given":"Pooja","family":"Biswas","sequence":"first","affiliation":[{"name":"Shiley Eye Institute, University of California San Diego, La Jolla, CA 92093, USA"},{"name":"School of Biotechnology, REVA University, Bengaluru 560064, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anne Marie","family":"Berry","sequence":"additional","affiliation":[{"name":"Shiley Eye Institute, University of California San Diego, La Jolla, CA 92093, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qais","family":"Zawaydeh","sequence":"additional","affiliation":[{"name":"Shiley Eye Institute, University of California San Diego, La Jolla, CA 92093, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dirk-Uwe G.","family":"Bartsch","sequence":"additional","affiliation":[{"name":"Shiley Eye Institute, University of California San Diego, La Jolla, CA 92093, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pongali B.","family":"Raghavendra","sequence":"additional","affiliation":[{"name":"School of Biotechnology, REVA University, Bengaluru 560064, India"},{"name":"National Institute of Biomedical Genomics, Kalyani 741251, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4788-0362","authenticated-orcid":false,"given":"J. Fielding","family":"Hejtmancik","sequence":"additional","affiliation":[{"name":"National Eye Institute, National Institute of Health, Bethesda, MD 20892, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4903-2065","authenticated-orcid":false,"given":"Naheed W.","family":"Khan","sequence":"additional","affiliation":[{"name":"Ophthalmology and Visual Sciences, University of Michigan Health, Michigan Medicine, Ann Arbor, MI 48109, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S. Amer","family":"Riazuddin","sequence":"additional","affiliation":[{"name":"Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, MD 20817, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Radha","family":"Ayyagari","sequence":"additional","affiliation":[{"name":"Shiley Eye Institute, University of California San Diego, La Jolla, CA 92093, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,8,17]]},"reference":[{"key":"ref_1","unstructured":"(2022, January 01). RetNet. Available online: http:\/\/www.sph.uth.tmc.edu\/Retnet\/."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"40","DOI":"10.1186\/1750-1172-1-40","article-title":"Retinitis pigmentosa","volume":"1","author":"Hamel","year":"2006","journal-title":"Orphanet J. Rare Dis."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"575","DOI":"10.1023\/A:1015183500719","article-title":"Molecular aspects of retinal degenerative diseases","volume":"21","author":"Lev","year":"2001","journal-title":"Cell Mol. Neurobiol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"238","DOI":"10.2174\/138920211795860107","article-title":"Retinitis pigmentosa: Genes and disease mechanisms","volume":"12","author":"Ferrari","year":"2011","journal-title":"Curr. Genom."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"132","DOI":"10.1111\/cge.12203","article-title":"Genes and mutations causing retinitis pigmentosa","volume":"84","author":"Daiger","year":"2013","journal-title":"Clin. Genet."},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Collin, G.B., Gogna, N., Chang, B., Damkham, N., Pinkney, J., Hyde, L.F., Stone, L., Naggert, J.K., Nishina, P.M., and Krebs, M.P. (2020). Mouse Models of Inherited Retinal Degeneration with Photoreceptor Cell Loss. Cells, 9.","DOI":"10.3390\/cells9040931"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"2030","DOI":"10.1038\/s41598-021-81414-1","article-title":"A new mouse model for retinal degeneration due to Fam161a deficiency","volume":"11","author":"Beryozkin","year":"2021","journal-title":"Sci. Rep."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1002\/9780470942390.mo150178","article-title":"Generating Mouse Models Using CRISPR-Cas9-Mediated Genome Editing","volume":"6","author":"Qin","year":"2016","journal-title":"Curr. Protoc. Mouse Biol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"357","DOI":"10.1016\/S0039-6257(02)00314-4","article-title":"Genetic animal models for retinal degeneration","volume":"47","author":"Fauser","year":"2002","journal-title":"Surv. Ophthalmol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"566","DOI":"10.1038\/eye.1998.146","article-title":"Animal models of human retinal dystrophies","volume":"12","year":"1998","journal-title":"Eye"},{"key":"ref_11","first-page":"2483","article-title":"A missense mutation in ASRGL1 is involved in causing autosomal recessive retinal degeneration","volume":"25","author":"Biswas","year":"2016","journal-title":"Hum. Mol. Genet."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"11026","DOI":"10.1021\/bi901397h","article-title":"The human asparaginase-like protein 1 hASRGL1 is an Ntn hydrolase with \u03b2-aspartyl peptidase activity","volume":"48","author":"Cantor","year":"2009","journal-title":"Biochemistry"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"910","DOI":"10.1016\/j.cell.2013.04.025","article-title":"One-step generation of mice carrying mutations in multiple genes by CRISPR\/Cas-mediated genome engineering","volume":"153","author":"Wang","year":"2013","journal-title":"Cell"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"5396","DOI":"10.1038\/srep05396","article-title":"Rapid generation of mouse models with defined point mutations by the CRISPR\/Cas9 system","volume":"4","author":"Inui","year":"2014","journal-title":"Sci. Rep."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"2000","DOI":"10.1093\/hmg\/ddr080","article-title":"A CTRP5 gene S163R mutation knock-in mouse model for late-onset retinal degeneration","volume":"20","author":"Chavali","year":"2011","journal-title":"Hum. Mol. Genet."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"5514","DOI":"10.1167\/iovs.06-0449","article-title":"Spatial and temporal expression of MFRP and its interaction with CTRP5","volume":"47","author":"Mandal","year":"2006","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1840","DOI":"10.1021\/cb300232n","article-title":"Uncoupling intramolecular processing and substrate hydrolysis in the N-terminal nucleophile hydrolase hASRGL1 by circular permutation","volume":"7","author":"Li","year":"2012","journal-title":"ACS Chem. Biol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"960","DOI":"10.1021\/acs.biochem.5b01157","article-title":"Intramolecular Cleavage of the hASRGL1 Homodimer Occurs in Two Stages","volume":"55","author":"Li","year":"2016","journal-title":"Biochemistry"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"529","DOI":"10.1016\/j.ygyno.2015.03.055","article-title":"Loss of ASRGL1 expression is an independent biomarker for disease-specific survival in endometrioid endometrial carcinoma","volume":"137","author":"Edqvist","year":"2015","journal-title":"Gynecol. Oncol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"3193","DOI":"10.1021\/acs.biochem.0c00354","article-title":"Improving the Treatment of Acute Lymphoblastic Leukemia","volume":"59","author":"Radadiya","year":"2020","journal-title":"Biochemistry"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"256","DOI":"10.3109\/10428194.2013.803224","article-title":"L-asparaginase: An effective agent in the treatment of acute lymphoblastic leukemia","volume":"55","author":"Kumar","year":"2014","journal-title":"Leuk Lymphoma"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"783547","DOI":"10.3389\/fcell.2021.783547","article-title":"Deletion of Asrgl1 Leads to Photoreceptor Degeneration in Mice","volume":"9","author":"Zhou","year":"2021","journal-title":"Front. Cell Dev. Biol."}],"container-title":["Genes"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2073-4425\/13\/8\/1461\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T00:10:52Z","timestamp":1760141452000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2073-4425\/13\/8\/1461"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,8,17]]},"references-count":22,"journal-issue":{"issue":"8","published-online":{"date-parts":[[2022,8]]}},"alternative-id":["genes13081461"],"URL":"https:\/\/doi.org\/10.3390\/genes13081461","relation":{},"ISSN":["2073-4425"],"issn-type":[{"value":"2073-4425","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,8,17]]}}}