Animal Modeling Core

About the Core

The Animal Modeling Core provides researchers with access to the latest technologies for hematologic studies in animal models.

The AMC offers expertise, technical assistance, and mice for human-into-mouse xenotransplantation studies. Mouse models include MITRG-SKI (KnockIn) mice that express human cytokines (M-CSF, IL-3, GM-CSF, THPO) and huSIRPα from the endogenous murine loci in the Rag-/- IL-2Rγ -/- background.

MI(S)TRG mice are maintained as separate MITRG and MITRG-SKI colonies to generate MISTRG mice that are heterozygous for the huSIRPα gene.

The AMC also offers training and technical assistance in the study of hematopoiesis and benign hematologic questions in mice.

Through the Yale Hematology Tissue Bank we are also able to offer primary patient samples.

For more information contact us and refer to the references below:

Consult with Us!

We suggest consultation with us prior to submitting an application to ensure ideal study design and to predict feasibility.

Please note that certain research may require material transfer agreements which may delay initiation of research. The YCCEH-AMC operates on a fee for service model and all fees reflect the actual expenses of cost recovery in providing services.

Review our Fee for Services Documentation

Request Services from YCCEH AMC

Read and complete the requests outlined in the YCCEH Animal Modeling Core (AMC) Service Request
Fill in and complete the YCCEH-AMC Biospecimen and Service Request Agreement.

Request Samples from Yale Hematology Tissue Bank

Read and complete the requests outlined in the Yale Hematology Tissue Bank Request of Services and Registration
Fill in and complete the Yale Hematology Tissue Bank (YHTB) Biospecimen and Data Request Agreement

News and Updates

For a MISTRG MTA submit a request to Regeneron’s preclinical research collaborations site.
If you wish to hear more about the latest developments in humanized mice watch the Meet-the-Expert presentation by Dr. Halene on the study of human hematopoiesis in humanized mice and read about the latest publication on the rescue of human red cells via combined cytokine-liver humanization.

Publications

2023

IL-6 trans-signaling in a humanized mouse model of scleroderma.Odell ID, Agrawal K, Sefik E, Odell AV, Caves E, Kirkiles-Smith NC, Horsley V, Hinchcliff M, Pober JS, Kluger Y, Flavell RA. Proc Natl Acad Sci U S A. 2023 Sep 12; 2023 Sep 5. PMID: 37669366.
Humanized mouse liver reveals endothelial control of essential hepatic metabolic functions.Kaffe E, Roulis M, Zhao J, Qu R, Sefik E, Mirza H, Zhou J, Zheng Y, Charkoftaki G, Vasiliou V, Vatner DF, Mehal WZ, Yuval Kluger, Flavell RA. Cell. 2023 Aug 31; 2023 Aug 9. PMID: 37562401.
Autologous humanized PDX modeling for immuno-oncology recapitulates features of the human tumor microenvironment.Chiorazzi M, Martinek J, Krasnick B, Zheng Y, Robbins KJ, Qu R, Kaufmann G, Skidmore Z, Juric M, Henze LA, Brösecke F, Adonyi A, Zhao J, Shan L, Sefik E, Mudd J, Bi Y, Goedegebuure SP, Griffith M, Griffith O, Oyedeji A, Fertuzinhos S, Garcia-Milian R, Boffa D, Detterbeck F, Dhanasopon A, Blasberg J, Judson B, Gettinger S, Politi K, Kluger Y, Palucka K, Fields RC, Flavell RA. J Immunother Cancer. 2023 Jul. PMID: 37487666.
An agenda to advance research in myelodysplastic syndromes: a TOP 10 priority list from the first international workshop in MDS.Stahl M, Abdel-Wahab O, Wei AH, Savona MR, Xu ML, Xie Z, Taylor J, Starczynowski D, Sanz GF, Sallman DA, Santini V, Roboz GJ, Patnaik MM, Padron E, Odenike O, Nazha A, Nimer SD, Majeti R, Little RF, Gore S, List AF, Kutchroo V, Komrokji RS, Kim TK, Kim N, Hourigan CS, Hasserjian RP, Halene S, Griffiths EA, Greenberg PL, Figueroa M, Fenaux P, Efficace F, DeZern AE, Della Porta MG, Daver NG, Churpek JE, Carraway HE, Brunner AM, Borate U, Bennett JM, Bejar R, Boultwood J, Loghavi S, Bewersdorf JP, Platzbecker U, Steensma DP, Sekeres MA, Buckstein RJ, Zeidan AM. Blood Adv. 2023 Jun 27. PMID: 36260702.
Humanized MISTRG as a preclinical in vivo model to study human neutrophil-mediated immune processes.Martinez-Sanz P, Laurent ARG, Slot E, Hoogenboezem M, Bąbała N, van Bruggen R, Rongvaux A, Flavell RA, Tytgat GAM, Franke K, Matlung HL, Kuijpers TW, Amsen D, Karrich JJ. Front Immunol. 2023; 2023 Mar 8. PMID: 36969261.
Selective inhibition of MCL1 overcomes venetoclax resistance in a murine model of myelodysplastic syndromes.Fischer MA, Song Y, Arrate MP, Gbyli R, Villaume MT, Smith BN, Childress MA, Stricker TP, Halene S, Savona MR. Haematologica. 2023 Feb 1; 2023 Feb 1. PMID: 35979721.

2022

Recruited monocytes/macrophages drive pulmonary neutrophilic inflammation and irreversible lung tissue remodeling in cystic fibrosis.Öz HH, Cheng EC, Di Pietro C, Tebaldi T, Biancon G, Zeiss C, Zhang PX, Huang PH, Esquibies SS, Britto CJ, Schupp JC, Murray TS, Halene S, Krause DS, Egan ME, Bruscia EM. Cell Rep. 2022 Dec 13. PMID: 36516754.
Targeting the EIF2AK1 Signaling Pathway Rescues Red Blood Cell Production in SF3B1-Mutant Myelodysplastic Syndromes With Ringed Sideroblasts.Adema V, Ma F, Kanagal-Shamanna R, Thongon N, Montalban-Bravo G, Yang H, Peslak SA, Wang F, Acha P, Sole F, Lockyer P, Cassari M, Maciejewski JP, Visconte V, Gañán-Gómez I, Song Y, Bueso-Ramos C, Pellegrini M, Tan TM, Bejar R, Carew JS, Halene S, Santini V, Al-Atrash G, Clise-Dwyer K, Garcia-Manero G, Blobel GA, Colla S. Blood Cancer Discov. 2022 Nov 2. PMID: 35926182.
Human neutrophil development and functionality are enabled in a humanized mouse model.Zheng Y, Sefik E, Astle J, Karatepe K, Öz HH, Solis AG, Jackson R, Luo HR, Bruscia EM, Halene S, Shan L, Flavell RA. Proc Natl Acad Sci U S A. 2022 Oct 25; 2022 Oct 21. PMID: 36269862.
Spatial profiling of chromatin accessibility in mouse and human tissues.Deng Y, Bartosovic M, Ma S, Zhang D, Kukanja P, Xiao Y, Su G, Liu Y, Qin X, Rosoklija GB, Dwork AJ, Mann JJ, Xu ML, Halene S, Craft JE, Leong KW, Boldrini M, Castelo-Branco G, Fan R. Nature. 2022 Sep; 2022 Aug 17. PMID: 35978191.
RNA m(6)A demethylase ALKBH5 regulates the development of γδ T cells.Ding C, Xu H, Yu Z, Roulis M, Qu R, Zhou J, Oh J, Crawford J, Gao Y, Jackson R, Sefik E, Li S, Wei Z, Skadow M, Yin Z, Ouyang X, Wang L, Zou Q, Su B, Hu W, Flavell RA, Li HB. Proc Natl Acad Sci U S A. 2022 Aug 16; 2022 Aug 8. PMID: 35939687.
Inflammasome activation in infected macrophages drives COVID-19 pathology.Sefik E, Qu R, Junqueira C, Kaffe E, Mirza H, Zhao J, Brewer JR, Han A, Steach HR, Israelow B, Blackburn HN, Velazquez SE, Chen YG, Halene S, Iwasaki A, Meffre E, Nussenzweig M, Lieberman J, Wilen CB, Kluger Y, Flavell RA. Nature. 2022 Jun; 2022 Apr 28. PMID: 35483404.
A humanized mouse model of chronic COVID-19.Sefik E, Israelow B, Mirza H, Zhao J, Qu R, Kaffe E, Song E, Halene S, Meffre E, Kluger Y, Nussenzweig M, Wilen CB, Iwasaki A, Flavell RA. Nat Biotechnol. 2022 Jun; 2021 Dec 17. PMID: 34921308.
In vivo anti-tumor effect of PARP inhibition in IDH1/2 mutant MDS/AML resistant to targeted inhibitors of mutant IDH1/2.Gbyli R, Song Y, Liu W, Gao Y, Biancon G, Chandhok NS, Wang X, Fu X, Patel A, Sundaram R, Tebaldi T, Mamillapalli P, Zeidan AM, Flavell RA, Prebet T, Bindra RS, Halene S. Leukemia. 2022 May; 2022 Mar 10. PMID: 35273342.
The Coming of Age of Preclinical Models of MDS.Liu W, Teodorescu P, Halene S, Ghiaur G. Front Oncol. 2022; 2022 Mar 16. PMID: 35372085.
DNMT3A R882 Mutations Confer Unique Clinicopathologic Features in MDS Including a High Risk of AML Transformation.Jawad M, Afkhami M, Ding Y, Zhang X, Li P, Young K, Xu ML, Cui W, Zhao Y, Halene S, Al-Kali A, Viswanatha D, Chen D, He R, Zheng G. Front Oncol. 2022; 2022 Feb 28. PMID: 35296003.
Development of Humanized Mouse Models for Studying Human NK Cells in Health and Disease.Shan L, Flavell RA, Herndler-Brandstetter D. Methods Mol Biol. 2022. PMID: 35344167.

2021

Transcriptome-wide quantification of double-stranded RNAs in live mouse tissues by dsRIP-Seq.Gao Y, Chen S, Halene S, Tebaldi T. STAR Protoc. 2021 Mar 19; 2021 Mar 18. PMID: 33778776.
A humanized mouse model of chronic COVID-19 to evaluate disease mechanisms and treatment options.Sefik E, Israelow B, Zhao J, Qu R, Song E, Mirza H, Kaffe E, Halene S, Meffre E, Kluger Y, Nussenzweig M, Wilen CB, Iwasaki A, Flavell RA. Res Sq. 2021 Mar 17; 2021 Mar 17. PMID: 33758831.
Combined liver-cytokine humanization comes to the rescue of circulating human red blood cells.Song Y, Shan L, Gbyli R, Liu W, Strowig T, Patel A, Fu X, Wang X, Xu ML, Gao Y, Qin A, Bruscia EM, Tebaldi T, Biancon G, Mamillapalli P, Urbonas D, Eynon E, Gonzalez DG, Chen J, Krause DS, Alderman J, Halene S, Flavell RA. Science. 2021 Mar 5. PMID: 33674488.

2020

The role of RNA epigenetic modification in normal and malignant hematopoiesis.Vasic R, Gao Y, Liu C, Halene S. Curr Stem Cell Rep. 2020 Dec; 2020 Aug 12. PMID: 33777659.
m(6)A Modification Prevents Formation of Endogenous Double-Stranded RNAs and Deleterious Innate Immune Responses during Hematopoietic Development.Gao Y, Vasic R, Song Y, Teng R, Liu C, Gbyli R, Biancon G, Nelakanti R, Lobben K, Kudo E, Liu W, Ardasheva A, Fu X, Wang X, Joshi P, Lee V, Dura B, Viero G, Iwasaki A, Fan R, Xiao A, Flavell RA, Li HB, Tebaldi T, Halene S. Immunity. 2020 Jun 16; 2020 Jun 3. PMID: 32497523.
Humanized mice as preclinical models for myeloid malignancies.Gbyli R, Song Y, Halene S. Biochem Pharmacol. 2020 Apr; 2020 Jan 10. PMID: 31926939.
Functional Analysis of Human Hematopoietic Stem Cells In Vivo in Humanized Mice.Song Y, Gbyli R, Fu X, Halene S. Methods Mol Biol. 2020. PMID: 31776933.

2019

A highly efficient and faithful MDS patient-derived xenotransplantation model for pre-clinical studies.Song Y, Rongvaux A, Taylor A, Jiang T, Tebaldi T, Balasubramanian K, Bagale A, Terzi YK, Gbyli R, Wang X, Fu X, Gao Y, Zhao J, Podoltsev N, Xu M, Neparidze N, Wong E, Torres R, Bruscia EM, Kluger Y, Manz MG, Flavell RA, Halene S. Nat Commun. 2019 Jan 21; 2019 Jan 21. PMID: 30664659.

2017

Humanized mouse model supports development, function, and tissue residency of human natural killer cells.Herndler-Brandstetter D, Shan L, Yao Y, Stecher C, Plajer V, Lietzenmayer M, Strowig T, de Zoete MR, Palm NW, Chen J, Blish CA, Frleta D, Gurer C, Macdonald LE, Murphy AJ, Yancopoulos GD, Montgomery RR, Flavell RA. Proc Natl Acad Sci U S A. 2017 Nov 7; 2017 Oct 25. PMID: 29078283.
A novel humanized mouse model with significant improvement of class-switched, antigen-specific antibody production.Yu H, Borsotti C, Schickel JN, Zhu S, Strowig T, Eynon EE, Frleta D, Gurer C, Murphy AJ, Yancopoulos GD, Meffre E, Manz MG, Flavell RA. Blood. 2017 Feb 23; 2017 Jan 11. PMID: 28077418.

2016

Microenvironment-dependent growth of preneoplastic and malignant plasma cells in humanized mice.Das R, Strowig T, Verma R, Koduru S, Hafemann A, Hopf S, Kocoglu MH, Borsotti C, Zhang L, Branagan A, Eynon E, Manz MG, Flavell RA, Dhodapkar MV. Nat Med. 2016 Nov; 2016 Oct 10. PMID: 27723723.
Peripheral blood CD34(+) cells efficiently engraft human cytokine knock-in mice.Saito Y, Ellegast JM, Rafiei A, Song Y, Kull D, Heikenwalder M, Rongvaux A, Halene S, Flavell RA, Manz MG. Blood. 2016 Oct 6; 2016 Aug 19. PMID: 27543436.

2015

Broad CTL response is required to clear latent HIV-1 due to dominance of escape mutations.Deng K, Pertea M, Rongvaux A, Wang L, Durand CM, Ghiaur G, Lai J, McHugh HL, Hao H, Zhang H, Margolick JB, Gurer C, Murphy AJ, Valenzuela DM, Yancopoulos GD, Deeks SG, Strowig T, Kumar P, Siliciano JD, Salzberg SL, Flavell RA, Shan L, Siliciano RF. Nature. 2015 Jan 15; 2015 Jan 7. PMID: 25561180.

2014

Development and function of human innate immune cells in a humanized mouse model.Rongvaux A, Willinger T, Martinek J, Strowig T, Gearty SV, Teichmann LL, Saito Y, Marches F, Halene S, Palucka AK, Manz MG, Flavell RA. Nat Biotechnol. 2014 Apr; 2014 Mar 16. PMID: 24633240.

2013

Human hemato-lymphoid system mice: current use and future potential for medicine.Rongvaux A, Takizawa H, Strowig T, Willinger T, Eynon EE, Flavell RA, Manz MG. Annu Rev Immunol. 2013; 2013 Jan 16. PMID: 23330956.

2011

Efficient differentiation and function of human macrophages in humanized CSF-1 mice.Rathinam C, Poueymirou WT, Rojas J, Murphy AJ, Valenzuela DM, Yancopoulos GD, Rongvaux A, Eynon EE, Manz MG, Flavell RA. Blood. 2011 Sep 15; 2011 Jul 25. PMID: 21791433.
Transgenic expression of human signal regulatory protein alpha in Rag2-/-gamma(c)-/- mice improves engraftment of human hematopoietic cells in humanized mice.Strowig T, Rongvaux A, Rathinam C, Takizawa H, Borsotti C, Philbrick W, Eynon EE, Manz MG, Flavell RA. Proc Natl Acad Sci U S A. 2011 Aug 9; 2011 Jul 25. PMID: 21788509.
Improving human hemato-lymphoid-system mice by cytokine knock-in gene replacement.Willinger T, Rongvaux A, Strowig T, Manz MG, Flavell RA. Trends Immunol. 2011 Jul; 2011 Jun 21. PMID: 21697012.
Human thrombopoietin knockin mice efficiently support human hematopoiesis in vivo.Rongvaux A, Willinger T, Takizawa H, Rathinam C, Auerbach W, Murphy AJ, Valenzuela DM, Yancopoulos GD, Eynon EE, Stevens S, Manz MG, Flavell RA. Proc Natl Acad Sci U S A. 2011 Feb 8; 2011 Jan 24. PMID: 21262827.
Human IL-3/GM-CSF knock-in mice support human alveolar macrophage development and human immune responses in the lung.Willinger T, Rongvaux A, Takizawa H, Yancopoulos GD, Valenzuela DM, Murphy AJ, Auerbach W, Eynon EE, Stevens S, Manz MG, Flavell RA. Proc Natl Acad Sci U S A. 2011 Feb 8; 2011 Jan 24. PMID: 21262803.