View source for Mouse Models of Human Cancer database

{{Infobox biodatabase
|title = Mouse Models of Human Cancer database
|logo = 
[[File:MMHCdb Logo.jpg|thumb| center|300px|]]
|description = Resource for information on mouse models of human cancer.
|scope = Mouse models, genetics, genomics, tumor pathology images.
|organism = ''Mus musculus, Homo sapiens''
|center = The Jackson Laboratory
|laboratory =
|author = 
|citation = Krupke et al. (2017)  PMID: 29092943
|pmid = 
|released = 
|standard = 
|format = 
|url = http://www.tumor.informatics.jax.org/
|download = 
|versioning = 
|frequency = 
|curation = 
|bookmark =
|version =
}}

The [[Organization:Laboratory mouse|laboratory mouse]] has been instrumental in investigating the genetics of human disease, including cancer, for over 110 years.<ref>{{cite journal |last1=Naf |first1=Dieter |title=The mouse tumor biology database: a public resource for cancer genetics and pathology of the mouse. |journal=Cancer Res |date=Mar 2002 |volume=62 |issue=5 |pages=1235–40 |pmid=11888882 |url=https://cancerres.aacrjournals.org/content/canres/62/5/1235.full.pdf |accessdate=18 February 2020}}</ref> The laboratory mouse has physiology and genetic characteristics very similar to humans providing powerful models for investigation of the genetic characteristics of disease.<ref>{{cite journal |last1=Justice |first1=M.J. |title=Technical approaches for mouse models of human disease |journal=Dis. Models Mech. |date=2011 |volume=4 |issue=3 |pages=305–10 |doi=10.1242/dmm.000901 |pmid=21558063 |pmc=3097452 }}</ref>

The '''Mouse Models of Human Cancer database (MMHCdb)''' is a unique, comprehensive online knowledgebase of mouse models of human [[Medicine:Cancer|cancer]] hosted by The [[Organization:Jackson Laboratory|Jackson Laboratory]] with funding from the [[Organization:National Cancer Institute|National Cancer Institute (NCI)]].<ref>{{cite web|url=http://www.informatics.jax.org/mgihome/other/mgi_funding.shtml|title=MGI-MGI Current Funding Support|work=jax.org|accessdate=14 Feb 2020}}</ref> MMHCdb is part of the [[Biology:Mouse Genome Informatics|Mouse Genome Informatics]] consortium (MGI) and was first released in 1998 as the Mouse Tumor Biology (MTB) database.<ref>{{cite journal |last1=Bult |first1=C.J. |title=Electronic access to mouse tumor data: the Mouse Tumor Biology Database (MTB) project. |journal=Nucleic Acids Res. |date=1999 |volume=27 |issue=1 |pages=99–105 |doi=10.1093/nar/27.1.99 |pmid=9847151 |pmc=148106 |url=}}</ref> MMHCdb  contains genetic and genomic information about [[Biology:Inbred strain|inbred mouse strains]], genetically engineered mouse models (GEMMs) and [[Medicine:Patient derived xenograft|Patient Derived Xenograft (PDX)]] models of human cancer. Data in MMHCdb is expertly curated from peer-reviewed scientific publications or obtained as direct data submissions from individual investigators and large-scale research initiatives.<ref>{{cite journal |last1=Krupke |first1=Debra |title=The Mouse Tumor Biology Database: A Comprehensive Resource for Mouse Models of Human Cancer. |journal=Cancer Res |date=Oct 2017 |volume=77 |issue=21 |pages=e67–e70 |doi=10.1158/0008-5472.CAN-17-0584 |pmid=29092943 |pmc=5679300 |url=}}</ref> MMHCdb, in collaboration with EMBL-EBI, co-developed the PDX Finder resource which serves as a global catalog of PDX models.<ref>{{cite journal |last1=Conte |first1=N |title=PDX Finder: A portal for patient-derived xenograft model discovery. |journal=Nucleic Acids Res. |date=Jan 2019 |volume=8 |issue=47(D1) |pages=D1073–D1079 |doi=10.1093/nar/gky984 |pmid=30535239 |pmc=6323912 }}</ref>

== Inbred Mouse Models==

Inbred mouse strains are the result of at least 20 generations of successive brother/sister matings which lead to a population with minimal segregating genetic variation. Inbred strains of mice allow researchers to investigate the role that genetics plays in cancer susceptibility and treatment response.  The first inbred strain, DBA (dilute brown agouti), was developed in 1909.<ref>{{cite journal |last1=Little |first1=C.C. |title=Further experimental studies on the inheritance of susceptibility to a transplantable tumor, carcinoma (J.w.A.) of the Japanese waltzing mouse. |journal=J. Med. Res. |date=1916 |volume=33 |issue=3 |pages=393–453 |pmid=19972275 |pmc=2083849 }}</ref> Among the earliest references to the use of inbred mice in cancer was the observed susceptibility of the A family of inbred mice to spontaneous lung tumors.<ref>{{cite journal |last1=Tyzzer |first1=E.E. |title=A series of spontaneous tumors in mice with observations on the influence of heredity on the frequency of their occurrence. | journal=J. Med. Res. |date=1909 |volume=21 |issue=3 |pages=479–518.13 |pmid=19971929 |pmc=2099039 }}</ref> MMHCdb provides interactive graphical summaries of the characteristic cancers observed in over 700 different inbred mouse strains. Figure 1 shows one of these tools, the Tumor Frequency Grid, which displays the frequency of different types of tumors across different inbred strains. 

[[File:TumorGridWiki.jpg|thumb|center|400px|[http://tumor.informatics.jax.org/mtbwi/dynamicGrid.do Fig. 1. Dynamic Tumor Frequency Grid.]]]

== Genetically Engineered Mouse Models (GEMMs) ==

[[Biology:Molecular biology|Molecular biology]] and [[Biology:Genome editing|genome editing]] technologies transformed the use of mice in cancer research by allowing researchers to develop animal models with specific mutations or that expressed human genes (transgenics).  The genetic background of genetically modified animals can influence the observed phenotypes and must be taken into account when mouse models of human cancer are developed and when interpreting the data generated by these models.  For example, transgenic mice on a mixed C57BL/6J and SJL background expressing human [[Biology:HRAS|HRAS]] have a mammary gland [[Medicine:Carcinoma|carcinoma]] frequency of 45-50% whereas the same [[Biology:Transgene|transgene]] expressed in FVB/N mice result in 100% of the animals having mammary gland carcinomas.<ref>{{cite journal |last1=Bult |first1=C.J. |title=Mouse Tumor Biology (MTB): a database of mouse models for human cancer. |journal=Nucleic Acids Research |date=Jan 2015 |volume=43 |issue=D1 |pages=D818-24 |doi=10.1093/nar/gku987 |pmid=25332399 |pmc=4384039 }}</ref>  MMHCdb provides search tools and displays to show the tumor frequencies of similar genetic modifications on different genetic backgrounds. Fig.2 shows the results of a search for lung adenocarcinomas with pathology images using the Faceted Search page and links to the results of that search.

[[File:Faceted Search example.jpg|thumb|center|400px|[http://tumor.informatics.jax.org/mtbwi/facetedSearch.do?start=0&fq=organParent%3ALung&fq=tcParent%3Aadenocarcinoma&fq=pathologyImages:%5b*%20TO%20*%5d Fig. 2. Faceted Search example.]]]

== Patient Derived Xenograft models (PDX) ==

A Patient Derived Xenograft (PDX) is generated by the implantation of human tumor tissue in an immunodeficient or [[Biology:Humanized|humanized]] host mouse strain. PDXs are a powerful pre-clinical model system for evaluating efficacy of cancer therapy.<ref>{{cite journal |last1=Zhou |first1=G. |title=Humanized NOD-SCID IL2rg(-/-) mice as a preclinical model for cancer research and its potential use for individualized cancer therapies. |journal=Cancer Lett. |date=2014 |volume=344 |issue=1 |pages=13–19 |doi=10.1016/j.canlet.2013.10.015 |pmid=24513265 }}</ref> Most of the PDX models in MMHCdb are from xenografts in the immunodeficient NSG host strain (aka, NOD scid gamma;  NOD.Cg-Prkdc<scid> Il2rg<tm1>Wjl/SzJ) mice developed at The Jackson Laboratory.<ref>{{cite journal |last1=Shultz |first1=L.D. |title=Humanized mice in translational biomedical research |journal=Nat. Rev. Immunol. |date=Feb 2007 |volume=7 |issue=2 |pages=118–30 |doi=10.1038/nri2017 |pmid=17259968 |s2cid=7933096 }}</ref>  MMHCdb allows researchers to search for PDX models by such parameters as cancer site, diagnosis, genomic properties of the engrafted human tumor, and model treatment response. Fig. 3 shows the output of a search for PDX models whose engrafted tumors have amplified KRAS, the TP53 A159V mutation, a deletion of the ALB gene, and high KIT expression. 

MMHCdb and EMBL-EBI co-developed PDX Finder, an searchable catalog of PDX models available from repositories around the world. 

[[File:PDX Like Me.jpg|thumb|center|400px|[http://bhmtbdb01.jax.org/mtbwi/pdxLikeMe.do Fig. 3. PDX Like Me search example.]]]

== Database content ==

The MMHCdb contains a large amount of varied, highly detailed data and is continually adding new data and data types. This section contains a summary of the content in MMHCdb as of February 2020;

{| class="wikitable"
|-
! Data Type !! Content
|-
| Data Sources|| 17413
|-
| Inbred strains|| 727
|-
| GEMMs|| 5695
|-
| PDX Models (PDX Finder)|| >2000
|-
| Models (strain + tumor type)|| 102296
|-
| Pathology Images|| 6452
|}

== See also ==

*[[Organization:Jackson Laboratory|The Jackson Laboratory]]
*[[Biology:Mouse Genome Informatics|Mouse Genome Informatics]]
*[[Organization:National Cancer Institute|National Cancer Institute]]
*American Association for Cancer Research

== References ==
{{reflist}}

== External links ==

*[http://tumor.informatics.jax.org/mtbwi/index.do MMHCdb]
*[http://www.informatics.jax.org/ MGI]
*[https://www.jax.org/ The Jackson Laboratory]
*[http://www.pdxfinder.org/ PDXFinder]
*[https://www.youtube.com/watch?v=yxkaabIH7Ns MMHCdb Tutorial]
*[https://www.jax.org/jax-mice-and-services/customer-support/technical-support/genetics-and-nomenclature NOMENCLATURE FOR MOUSE STRAINS]



[[Category:Cancer research]]
[[Category:Databases]]

{{Sourceattribution|Mouse Models of Human Cancer database|1}}