Spontaneous early-onset neurodegeneration in the brainstem and spinal cord of NSG, NOG, and NXG mice
The spectrum of background, incidental, and experimentally induced lesions affecting NSG and NOG mice has been the subject of intense investigation. However, comprehensive studies focusing on the spontaneous neuropathological changes of these immunocompromised strains are lacking. This work describe...
Uloženo v:
| Vydáno v: | Veterinary pathology Ročník 60; číslo 3; s. 374 |
|---|---|
| Hlavní autoři: | , , , , , , , , , |
| Médium: | Journal Article |
| Jazyk: | angličtina |
| Vydáno: |
United States
01.05.2023
|
| Témata: | |
| ISSN: | 1544-2217, 1544-2217 |
| On-line přístup: | Zjistit podrobnosti o přístupu |
| Tagy: |
Přidat tag
Žádné tagy, Buďte první, kdo vytvoří štítek k tomuto záznamu!
|
| Abstract | The spectrum of background, incidental, and experimentally induced lesions affecting NSG and NOG mice has been the subject of intense investigation. However, comprehensive studies focusing on the spontaneous neuropathological changes of these immunocompromised strains are lacking. This work describes the development of spontaneous early-onset neurodegeneration affecting both juvenile and adult NSG, NOG, and NXG mice. The study cohort consisted of 367 NSG mice of both sexes (including 33 NSG-SGM3), 61 NOG females (including 31 NOG-EXL), and 4 NXG females. These animals were primarily used for preclinical CAR T-cell testing, generation of humanized immune system chimeras, and/or tumor xenograft transplantation. Histopathology of brain and spinal cord and immunohistochemistry (IHC) for AIF-1, GFAP, CD34, and CD45 were performed. Neurodegenerative changes were observed in 57.6% of the examined mice (affected mice age range was 6-36 weeks). The lesions were characterized by foci of vacuolation with neuronal degeneration/death and gliosis distributed throughout the brainstem and spinal cord. IHC confirmed the development of gliosis, overexpression of CD34, and a neuroinflammatory component comprised of CD45-positive monocyte-derived macrophages. Lesions were significantly more frequent and severe in NOG mice. NSG males were considerably more affected than NSG females. Increased lesion frequency and severity in older animals were also identified. These findings suggest that NSG, NOG, and NXG mice are predisposed to the early development of identical neurodegenerative changes. While the cause of these lesions is currently unclear, potential associations with the genetic mutations shared by NSG, NOG, and NXG mice as well as unidentified viral infections are considered. |
|---|---|
| AbstractList | The spectrum of background, incidental, and experimentally induced lesions affecting NSG and NOG mice has been the subject of intense investigation. However, comprehensive studies focusing on the spontaneous neuropathological changes of these immunocompromised strains are lacking. This work describes the development of spontaneous early-onset neurodegeneration affecting both juvenile and adult NSG, NOG, and NXG mice. The study cohort consisted of 367 NSG mice of both sexes (including 33 NSG-SGM3), 61 NOG females (including 31 NOG-EXL), and 4 NXG females. These animals were primarily used for preclinical CAR T-cell testing, generation of humanized immune system chimeras, and/or tumor xenograft transplantation. Histopathology of brain and spinal cord and immunohistochemistry (IHC) for AIF-1, GFAP, CD34, and CD45 were performed. Neurodegenerative changes were observed in 57.6% of the examined mice (affected mice age range was 6-36 weeks). The lesions were characterized by foci of vacuolation with neuronal degeneration/death and gliosis distributed throughout the brainstem and spinal cord. IHC confirmed the development of gliosis, overexpression of CD34, and a neuroinflammatory component comprised of CD45-positive monocyte-derived macrophages. Lesions were significantly more frequent and severe in NOG mice. NSG males were considerably more affected than NSG females. Increased lesion frequency and severity in older animals were also identified. These findings suggest that NSG, NOG, and NXG mice are predisposed to the early development of identical neurodegenerative changes. While the cause of these lesions is currently unclear, potential associations with the genetic mutations shared by NSG, NOG, and NXG mice as well as unidentified viral infections are considered.The spectrum of background, incidental, and experimentally induced lesions affecting NSG and NOG mice has been the subject of intense investigation. However, comprehensive studies focusing on the spontaneous neuropathological changes of these immunocompromised strains are lacking. This work describes the development of spontaneous early-onset neurodegeneration affecting both juvenile and adult NSG, NOG, and NXG mice. The study cohort consisted of 367 NSG mice of both sexes (including 33 NSG-SGM3), 61 NOG females (including 31 NOG-EXL), and 4 NXG females. These animals were primarily used for preclinical CAR T-cell testing, generation of humanized immune system chimeras, and/or tumor xenograft transplantation. Histopathology of brain and spinal cord and immunohistochemistry (IHC) for AIF-1, GFAP, CD34, and CD45 were performed. Neurodegenerative changes were observed in 57.6% of the examined mice (affected mice age range was 6-36 weeks). The lesions were characterized by foci of vacuolation with neuronal degeneration/death and gliosis distributed throughout the brainstem and spinal cord. IHC confirmed the development of gliosis, overexpression of CD34, and a neuroinflammatory component comprised of CD45-positive monocyte-derived macrophages. Lesions were significantly more frequent and severe in NOG mice. NSG males were considerably more affected than NSG females. Increased lesion frequency and severity in older animals were also identified. These findings suggest that NSG, NOG, and NXG mice are predisposed to the early development of identical neurodegenerative changes. While the cause of these lesions is currently unclear, potential associations with the genetic mutations shared by NSG, NOG, and NXG mice as well as unidentified viral infections are considered. The spectrum of background, incidental, and experimentally induced lesions affecting NSG and NOG mice has been the subject of intense investigation. However, comprehensive studies focusing on the spontaneous neuropathological changes of these immunocompromised strains are lacking. This work describes the development of spontaneous early-onset neurodegeneration affecting both juvenile and adult NSG, NOG, and NXG mice. The study cohort consisted of 367 NSG mice of both sexes (including 33 NSG-SGM3), 61 NOG females (including 31 NOG-EXL), and 4 NXG females. These animals were primarily used for preclinical CAR T-cell testing, generation of humanized immune system chimeras, and/or tumor xenograft transplantation. Histopathology of brain and spinal cord and immunohistochemistry (IHC) for AIF-1, GFAP, CD34, and CD45 were performed. Neurodegenerative changes were observed in 57.6% of the examined mice (affected mice age range was 6-36 weeks). The lesions were characterized by foci of vacuolation with neuronal degeneration/death and gliosis distributed throughout the brainstem and spinal cord. IHC confirmed the development of gliosis, overexpression of CD34, and a neuroinflammatory component comprised of CD45-positive monocyte-derived macrophages. Lesions were significantly more frequent and severe in NOG mice. NSG males were considerably more affected than NSG females. Increased lesion frequency and severity in older animals were also identified. These findings suggest that NSG, NOG, and NXG mice are predisposed to the early development of identical neurodegenerative changes. While the cause of these lesions is currently unclear, potential associations with the genetic mutations shared by NSG, NOG, and NXG mice as well as unidentified viral infections are considered. |
| Author | Radaelli, Enrico Verrelle, Jillian Sprengers, Justin Lanza, Matthew Willis, Elinor Banerjee, Esha Hermans, Els Tarrant, James Carmine Finesso, Giovanni Assenmacher, Charles-Antoine |
| Author_xml | – sequence: 1 givenname: Giovanni surname: Finesso fullname: Finesso, Giovanni organization: Comparative Pathology Core, Department of Pathobiology, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA, USA – sequence: 2 givenname: Elinor surname: Willis fullname: Willis, Elinor organization: Comparative Pathology Core, Department of Pathobiology, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA, USA – sequence: 3 givenname: James Carmine surname: Tarrant fullname: Tarrant, James Carmine organization: GlaxoSmithKline, Collegeville, PA, USA – sequence: 4 givenname: Matthew surname: Lanza fullname: Lanza, Matthew organization: Penn State University, Hershey, PA, USA – sequence: 5 givenname: Justin surname: Sprengers fullname: Sprengers, Justin organization: Netherlands Cancer Institute, Amsterdam, The Netherlands – sequence: 6 givenname: Jillian surname: Verrelle fullname: Verrelle, Jillian organization: Comparative Pathology Core, Department of Pathobiology, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA, USA – sequence: 7 givenname: Esha surname: Banerjee fullname: Banerjee, Esha organization: Comparative Pathology Core, Department of Pathobiology, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA, USA – sequence: 8 givenname: Els surname: Hermans fullname: Hermans, Els organization: Netherlands Cancer Institute, Amsterdam, The Netherlands – sequence: 9 givenname: Charles-Antoine orcidid: 0000-0003-0073-2730 surname: Assenmacher fullname: Assenmacher, Charles-Antoine organization: Comparative Pathology Core, Department of Pathobiology, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA, USA – sequence: 10 givenname: Enrico orcidid: 0000-0002-2885-0221 surname: Radaelli fullname: Radaelli, Enrico organization: Comparative Pathology Core, Department of Pathobiology, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA, USA |
| BackLink | https://www.ncbi.nlm.nih.gov/pubmed/36727841$$D View this record in MEDLINE/PubMed |
| BookMark | eNpNUEtLxDAYDLLiPvQHeJEcPVjNl0fTHkV0FZbdwyp4K2nzVSttUpP2sP_elV3By8zADAMzczJx3iEhl8BuAbS-Y4KxPFMZFwAKJBMnZAZKyoRz0JN_ekrmMX4xxnme6TMyFanmOpMwI3bbezcYh36MFE1od4l3EQfqcAze4gc6DGZovKONo8Mn0jKYxsUBO2qcpbFvnGlp5YOlvqbr7fKGrjd7-DXX70vaNRWek9PatBEvjrwgb0-Prw_PyWqzfHm4XyWV1HxIyj0Zo2pQKEUplEpznRttjeBSyopnVkipK0hBWywV8hq4wIylRpQ8l4ovyPWhtw_-e8Q4FF0TK2zbw76Caw25yKWEffTqGB3LDm3Rh6YzYVf8PcN_AGjcZfk |
| CitedBy_id | crossref_primary_10_1002_alz_70084 crossref_primary_10_1002_ame2_12509 crossref_primary_10_1016_j_molmed_2024_07_005 crossref_primary_10_1177_03009858241279141 crossref_primary_10_1177_03009858251372565 |
| ContentType | Journal Article |
| DBID | CGR CUY CVF ECM EIF NPM 7X8 |
| DOI | 10.1177/03009858231151403 |
| DatabaseName | Medline MEDLINE MEDLINE (Ovid) MEDLINE MEDLINE PubMed MEDLINE - Academic |
| DatabaseTitle | MEDLINE Medline Complete MEDLINE with Full Text PubMed MEDLINE (Ovid) MEDLINE - Academic |
| DatabaseTitleList | MEDLINE - Academic MEDLINE |
| Database_xml | – sequence: 1 dbid: NPM name: PubMed url: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed sourceTypes: Index Database – sequence: 2 dbid: 7X8 name: MEDLINE - Academic url: https://search.proquest.com/medline sourceTypes: Aggregation Database |
| DeliveryMethod | no_fulltext_linktorsrc |
| Discipline | Veterinary Medicine |
| EISSN | 1544-2217 |
| ExternalDocumentID | 36727841 |
| Genre | Journal Article Research Support, N.I.H., Extramural |
| GrantInformation_xml | – fundername: NCI NIH HHS grantid: P30 CA016520 – fundername: NIH HHS grantid: S10 OD023465 |
| GroupedDBID | --- -TM ..I .2E .2J .2N .GJ 01A 0R~ 123 1~K 2WC 31R 31U 31X 31Z 4.4 53G 54M 5RE 5VS AABMB AACKU AACMV AACTG AADUE AAEJI AAEWN AAGGD AAGLT AAGMC AAHBH AAJIQ AAJOX AAKGS AANSI AAPEO AAPII AAQXH AAQXI AARDL AARIX AATAA AATBZ AAUAS AAXOT AAYTG AAZBJ ABAWP ABCCA ABCJG ABDWY ABEIX ABFWQ ABHKI ABIDT ABJIS ABJNI ABJZC ABKRH ABLUO ABPGX ABPNF ABQKF ABQXT ABRHV ABUJY ABVFX ABVVC ABYTW ACARO ACDSZ ACDXX ACFEJ ACFMA ACFYK ACGBL ACGFO ACGFS ACGZU ACJER ACJTF ACLFY ACLHI ACLZU ACOFE ACOXC ACROE ACSIQ ACUAV ACUIR ACXKE ACXMB ADBBV ADDLC ADEBD ADEIA ADMPF ADNBR ADNON ADRRZ ADTBJ ADUKL ADVBO ADZZY AECGH AECVZ AEDTQ AEKYL AENEX AEPTA AEQLS AERKM AESZF AEUHG AEWDL AEWHI AEXFG AEXNY AFEET AFFNX AFKBI AFKRG AFMOU AFQAA AFUIA AGHKR AGKLV AGNHF AGPXR AGWFA AHDMH AHJOV AIGRN AJABX AJEFB AJGYC AJMMQ AJSCY AJUZI AJVBE AJXAJ ALKWR ALMA_UNASSIGNED_HOLDINGS AMCVQ ANDLU ARTOV AUTPY AUVAJ AYAKG B3H B8M B8R B8Z B94 BAWUL BBRGL BDDNI BKIIM BKSCU BPACV BSEHC BWJAD C1A CAG CBRKF CDWPY CFDXU CGR COF CORYS CQQTX CS3 CUTAK CUY CVF DB0 DC- DC. DC0 DD- DD0 DE- DE. DF0 DIK DN0 DO- DOPDO DU5 DV7 E3Z EBS ECGQY ECM EIF EJD EYRJQ F5P FHBDP GROUPED_SAGE_PREMIER_JOURNAL_COLLECTION H13 HF~ HZ~ J8X K.F MW2 N9A NPM NQS O9- P.9 P.B P2P Q1R Q7L Q7U Q83 ROL S01 SASJQ SAUOL SCNPE SFC SHG SPQ SPV TR2 TVP W8F WOQ ZGI ZONMY ZPPRI ZRKOI ZSSAH ZXP ~KM 7X8 AJHME |
| ID | FETCH-LOGICAL-c472t-bc47aa5f15e43b3556979a7da32444c28d3447c1617deb5e2f123e806a3b29452 |
| IEDL.DBID | 7X8 |
| ISICitedReferencesCount | 5 |
| ISICitedReferencesURI | http://www.webofscience.com/api/gateway?GWVersion=2&SrcApp=Summon&SrcAuth=ProQuest&DestLinkType=CitingArticles&DestApp=WOS_CPL&KeyUT=000924303800001&url=https%3A%2F%2Fcvtisr.summon.serialssolutions.com%2F%23%21%2Fsearch%3Fho%3Df%26include.ft.matches%3Dt%26l%3Dnull%26q%3D |
| ISSN | 1544-2217 |
| IngestDate | Thu Oct 02 04:07:43 EDT 2025 Mon Jul 21 05:53:49 EDT 2025 |
| IsDoiOpenAccess | false |
| IsOpenAccess | true |
| IsPeerReviewed | true |
| IsScholarly | true |
| Issue | 3 |
| Keywords | vacuolation NSG spontaneous lesion NOG neurodegeneration gliosis NXG CD34 |
| Language | English |
| LinkModel | DirectLink |
| MergedId | FETCHMERGED-LOGICAL-c472t-bc47aa5f15e43b3556979a7da32444c28d3447c1617deb5e2f123e806a3b29452 |
| Notes | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 |
| ORCID | 0000-0003-0073-2730 0000-0002-2885-0221 |
| OpenAccessLink | https://pubmed.ncbi.nlm.nih.gov/PMC10150263 |
| PMID | 36727841 |
| PQID | 2771939441 |
| PQPubID | 23479 |
| ParticipantIDs | proquest_miscellaneous_2771939441 pubmed_primary_36727841 |
| PublicationCentury | 2000 |
| PublicationDate | 2023-05-01 |
| PublicationDateYYYYMMDD | 2023-05-01 |
| PublicationDate_xml | – month: 05 year: 2023 text: 2023-05-01 day: 01 |
| PublicationDecade | 2020 |
| PublicationPlace | United States |
| PublicationPlace_xml | – name: United States |
| PublicationTitle | Veterinary pathology |
| PublicationTitleAlternate | Vet Pathol |
| PublicationYear | 2023 |
| SSID | ssj0022987 |
| Score | 2.3886313 |
| Snippet | The spectrum of background, incidental, and experimentally induced lesions affecting NSG and NOG mice has been the subject of intense investigation. However,... |
| SourceID | proquest pubmed |
| SourceType | Aggregation Database Index Database |
| StartPage | 374 |
| SubjectTerms | Animals Brain Stem Female Gliosis - veterinary Male Mice Mice, SCID Neoplasms - veterinary Spinal Cord |
| Title | Spontaneous early-onset neurodegeneration in the brainstem and spinal cord of NSG, NOG, and NXG mice |
| URI | https://www.ncbi.nlm.nih.gov/pubmed/36727841 https://www.proquest.com/docview/2771939441 |
| Volume | 60 |
| WOSCitedRecordID | wos000924303800001&url=https%3A%2F%2Fcvtisr.summon.serialssolutions.com%2F%23%21%2Fsearch%3Fho%3Df%26include.ft.matches%3Dt%26l%3Dnull%26q%3D |
| hasFullText | |
| inHoldings | 1 |
| isFullTextHit | |
| isPrint | |
| link | http://cvtisr.summon.serialssolutions.com/2.0.0/link/0/eLvHCXMwpV27TsMwFLWAMrDwKK_ykpEYiSC2EycTQoiWgYZKhSpb5NgO6pIEUvh-7nVSmJCQWJwhsuTYju-xz_U5hFxEkmkjROFBaOee8HEdFLHylObM14BoubsePXuUSRKlaTzpDtyaLq1yuSa6hdpUGs_Ir5iUgDViiN439ZuHrlHIrnYWGqukxwHKYEqXTL9ZBMZiZ5CHgjPQFl92rKYTXOKopBkgCQYxTzjPrF8Qpos0w63_tnGbbHYYk962k2KHrNiyT_ozTHxxt2_puCPUd4mZ1lUJ-NBWHw21KHbsYXr1gjqdS2NfnSo1Dh6dlxTAIs3RUwLVn6kqDW1qdNWiuIWlVUGT6eiSJk9Q4MskHVF0u98jL8P757sHrzNe8LSQbOHl8FAqKPzACp4DIgljGStpFKAvITSLDOoEatwaGZsHlhUQ_2x0HSqes1gEbJ-slVVpDwnNdZQXSkchD7nQAY_Dwl7nUWi0NCK0ckDOl12ZwcRGtqL95uynMwfkoB2PrG4VODKO_HEk_KM_1D4mG2gR3yYpnpBeAb-1PSXr-nMxb97P3IyBMpmMvwAe-cj1 |
| linkProvider | ProQuest |
| openUrl | ctx_ver=Z39.88-2004&ctx_enc=info%3Aofi%2Fenc%3AUTF-8&rfr_id=info%3Asid%2Fsummon.serialssolutions.com&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=Spontaneous+early-onset+neurodegeneration+in+the+brainstem+and+spinal+cord+of+NSG%2C+NOG%2C+and+NXG+mice&rft.jtitle=Veterinary+pathology&rft.au=Finesso%2C+Giovanni&rft.au=Willis%2C+Elinor&rft.au=Tarrant%2C+James+Carmine&rft.au=Lanza%2C+Matthew&rft.date=2023-05-01&rft.issn=1544-2217&rft.eissn=1544-2217&rft.volume=60&rft.issue=3&rft.spage=374&rft_id=info:doi/10.1177%2F03009858231151403&rft.externalDBID=NO_FULL_TEXT |
| thumbnail_l | http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/lc.gif&issn=1544-2217&client=summon |
| thumbnail_m | http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/mc.gif&issn=1544-2217&client=summon |
| thumbnail_s | http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/sc.gif&issn=1544-2217&client=summon |