Featured JAX® Mice for Cancer Research

Bladder

B6D2F1/J

100006
Cancer types: bladder

• Allograft model for bladder and other cancers

• Widely used for testing drug efficacy (Sun et al. 1996)

• Extensive phenotypic data available from the Mouse Phenome Database

Bone

B6;129S2-Nf2^tm1Tyj/J

008190
Cancer types: bone, lymph, lung, liver, fibrosarcoma

• Heterozygotes develop a variety of tumors over 10-30 months, including osteosarcoma (63%), lymphoma (15%), lung tumors (10%), hepatocellular carcinoma (9%), and fibrosarcoma (9%) (McClatchey et al. 1998)

• Incidence of osteosarcomas increases on 129S2 background and is higher in females than males (regardless of background)

• Tumors often metastasize to distant sites, such as the lung and liver

• Homozygotes fail by embryonic day 6.5-7.0, exhibiting a collapsed extraembryonic region

• May be used to study embryonic development and cancer

Brain

C57BL/6-Tg(Neurod2-Smo*A1)199Jols/J

008831
Cancer types: brain (medulloblastomas)

• Expresses the constitutively active mouse smoothened homolog in cerebellar granule cells (Hallahan et al. 2004)

• 48% of hemizygous mice develop medulloblastoma at 3-12 months (median 6)

• Homozygotes show higher tumor incidence and shorter latency (94% by 2 months; average age of onset is 4 months)

• Disease progresses to leptomeningeal metastasis of the brain and spine

Colon/Intestinal

B6.129P2-Il10^tm1Cgn/J

002251
Cancer types: colorectal and intestinal

• 13% of 9-week old mice have intestinal adenocarcinoma

• 65% of 10-31 week old mice have colorectal carcinoma (Sturlan et al. 2001)

C57BL/6J- Apc^Min/J

002020
Cancer types: intestinal and mammary

• Highly susceptible to spontaneous intestinal adenoma; median age of death from tumor burden: 118 +/- 26 days (about 4 months) (Moser et al. 1990)

• Tumor progression is genetic background-, diet-, and health status-dependent: B6 background is highly-susceptible; a higher polyp count is observed on a high fat diet; exposure to Helicobacter species hastens cancer progression (Moser et al. 1992; Mai et al. 2003; Halberg et al. 2009)

• Females may develop mammary tumors and are generally too sick to raise litters, becoming anemic and dying by four months (Moser et al. 1993)

• May carry a dominant modifier of Min (Mom2) gene that reduces polyp number and incidence (Silverman et al. 2002;Silverman et al. 2003)

ICR/HaJ

009122
Cancer type: colorectal

• Inbred strain derived from the outbred ICR/Ha
• 100% develop colon tumors (adenocarcinomas) by 24 weeks after subcutaneous injection of 1,2-dimethylhydrazine (DMH) (Jacoby et al. 1994)
• In contrast, the strain C57BL/6HaJ (009123) is resistant to DMH-induced colon cancer
• Carries the MHC haplotype H2g7 and may be used as a non-diabetic control for NOD/ShiLtJ (001976)
• Like outbred ICR, this inbred is highly prolific
• Useful in therapeutic drug testing
• Extensive phenotypic data available from the Mouse Phenome Database
• Historical characteristics: Festings

Kidney

B6;129S4-Tsc2^tm1Djk/J

004686
Cancer types: kidney, liver, lung and angiosarcoma

• Heterozygotes develop multiple bilateral renal cystadenoma by 12-15 months with 100% incidence (modeling tuberous sclerosis); homozygotes are embryonic lethal. (Onda et al. 1999)

• About 10% progress to renal carcinomas or extremity angiosarcoma

• Heterozygotes also develop liver hemangioma (more common in females than in males) and/or lung adenoma with a median latency of 15 months

Leukemia and Lymphoma

AKR/J

000648
Cancer types: leukemia

• Spontaneously develop leukemia with variable latency at 6-19 months (Hoag WG. 1963)

• Ubiquitously expresses the endogenous, ecotropic retrovirus AKV (Hartley et al. 1977; Lovmand et al. 1998)

• Extensive phenotypic data available from the Mouse Phenome Database

• Resequenced by the NIEHS-supported Resequencing Project

P/J

000679
Cancer types: leukemia

• 58% incidence of lymphatic leukemia in virgin females and about 22% incidence in males (Hoag WG. 1963)

• Highly susceptible to audiogenic and electroconvulsive seizures (Deckard et al. 1976)

• Extensive phenotypic data available from the Mouse Phenome Database

B6.129P2(Cg)-Mll1^{tm2(MLLT3)Thr}/KsyJ

009079
Cancer types: leukemia

• Mll-AF9 knock in allele mimics the t(9;11)(p22;q23) translocation found in patients (Coral et al. 1996; Chen et al. 2006)

• 61% develop leukemia by 5-12 months

• Predominantly acute myeloid leukemia (AML) involving immature myeloblasts and extramedullary leukemia, a minority is acute lymphoblastic leukemia (ALL)

B6.Cg-Tg(IghMyc)22Bri/J

002728
Cancer types: B-cell lymphoma

• Expresses the myelocytomatosis (Myc) oncogene in the B cell lineage

• High numbers of pre-B cells in the bone marrow throughout life and a transient increase in large pre-B cells in the blood at 3-4 weeks

• Pre-B and B cell lymphoma arise at a median age of 2.75 months (Adams et al. 1985)

• Model of human Burkitt Lymphoma (Keller et al. 2007)

• All tumors metastasize to the liver and/or lungs

B6.129S2-Trp53^tm1Tyj/J

002101
Cancer types: lymphoma and sarcoma

• Loss of Trp53 in double mutants accelerates tumor onset, shortens life span, and/or increases metastases (Jacks et al. 1994; Donehower et al. 1992; Elson A et al. 1995; Attardi and Donehower 2005)

• Homozygotes develop tumors by 3-6 months, principally lymphomas (56% incidence) and osteosarcomas

• Heterozygotes show a later onset (around 10 months): 32% incidence of lymphomas, 56% sarcomas and 12% carcinomas in several tissues

• Mouse model of human Li-Fraumeni syndrome, a form of familial breast cancer with TRP53 mutations (Elledge and Allred 1998)

CD1-Tg(Igh-HOX11)11Idd/J

003395
Cancer types: non-Hodgkin's lymphoma

• Transgenic for human HOX11, a homeodomain containing transcription factor, under the control of TCR alpha/delta regulatory elements (Hough et al. 1998)

• 85% develop B cell lymphoma and die by two years

• 13-19% of tumors metastasize to the liver and/or lungs

Liver

C3H/HeJ

000659
Cancer types: liver and mammary

• High incidence of hepatoma by 14 months: 72-91% in males, 59% in virgin females, 30-38% in breeding females (Dragani et al. 1995; Heston WE. 1963)

• Despite carrying no MMTV, virgin and breeding females may develop mammary tumors later in life (Outzen et al. 1985;Heston and Vlahakis 1971)

• Part of our unique Genetic Stability Program

• Resequenced by the NIEHS-supported Resequencing Project 

• Extensive phenotypic data available from the Mouse Phenome Database

B6;129S4-Plk3^tm1Dai/J

009691
Cancer types: liver, lung, kidney, uterus and intestine

• Aged mice develop well vascularized tumors in several organs (Yang et al. 2008)

• 19.2% incidence of liver tumors

• 30.8% incidence of lung carcinomas

• low incidence of tumors in kidney, uterus, and intestine

• Altered hypoxia-inducible factor 1α pathway involved in tumorigenesis

Lung

A/J 

000646 
Cancer types: lung and mammary

• Highly susceptible to spontaneous and carcinogen-induced lung tumors

• Primary lung tumors in: 6% in males, 26-32% in females

• High incidence of mammary adenocarcinoma in mated females (Hoag WG. 1963)

• Resequenced by the NIEHS-supported Resequencing Project (JAX® NOTES Issue 496, Winter 2005)

• Extensive phenotypic data available from the Mouse Phenome Database

B6.129S4-Kras^tm4Tyj/J

008179
Cancer types: lung

• Intranasal infection with adenoviral Cre results in very high frequency lung tumors (Ho et al. 2009; Jackson et al. 2001)

• 6-8 months after induction lung adenocarcinomas, papillary adenomas and bronchiolar hyperplasia and dysplasia develop

Mammary

FVB/N-Tg(MMTVneu)202Mul/J

002376
Cancer types: mammary

• Transgenic expression of unactivated rat Erbb2/Neu oncogene (Guy et al. 1992; Muller et al. 1996)

• Mammary tumors arise multifocally in hyperplastic mammary glands with variable latency (16-40 weeks; median age about 7 months)

• In 72% of mice over 8 months old, tumors metastasize to the lungs

• Model of HER2 / Erbb2 / Neu human breast cancer

FVB/N-Tg(MMTV-PyVT)634Mul/J

002374
Cancer types: mammary

• 100% of virgin and mated females develop mammary adenocarcinoma by five weeks; tumors are multifocal, highly fibrotic, and involve the entire mammary fat pad (Guy et al. 1992)

• Pulmonary metastases develop in 80%-94% of tumor-bearing females

• Females stop lactating when transgene is expressed

• Age of tumor onset and metastatic potential are genetic background-dependent (Lifsted et al. 1998)

• Phenotypic data available from the Mouse Phenome Database

B6.FVB-Tg(MMTV-PyVT)634Mul/LellJ

022974
Cancer types: mammary

• 100% of virgin and mated females develop mammary tumors by five months; tumor onset is delayed (by an average of 43 days) compared to the FVB background strain (002374) (Davie et al. 2007)
• Pulmonary metastases develop with reduced incidence, compared to FVB background strain (002374)
• Females stop lactating when transgene is expressed
• Age of tumor onset and incidence of metastases are genetic background-dependent (Lifsted et al. 1998; Davie et al. 2007)

FVB.Cg-Tg(MMTV-vHaras)SH1Led/J

004363
Cancer types: mammary, lymphoid, and salivary gland

• Mammary, lymphoid, and/or salivary gland tumors develop from as early as 5 weeks of age through 6 or more months (Andarawewa et al. 2003; Sinn et al. 1987)

• Tumorigenesis accelerated by pregnancy: tumors in parous females develop before 1st litter is weaned

• Tumors are locally invasive adenocarcinoma, some metastasizing to the liver and/or lungs

STOCK Trp53^tmBrd Brca1^tm1Aash Tg(LGB-cre)74Acl/J

012620
Cancer types: mammary

• Following two rounds of pregnancy 64% of mice develop mammary gland tumors (McCarthy et al. 2007)

• Tumors develop in inguinal and thoracic glands

• High grade ductal carcinoma in situ (DCIS) is observed admixed or adjacent to tumors

FVB-Tg(C3-1-Tag)cJeg/JegJ

013591
Cancer types: mammary (females) and prostate (males)

• Females develop multiple mammary ductal adenocarcinoma by 6 months (Maroulakou et al. 1994)

• 10% of females mice exhibit lung metastasis at 6 months

• 100% of males develop high grade prostatic intraepithelial neoplasia in ventral prostate at 4-12 months

• 19% of males exhibit carcinoma by 7 months

GR/J

006131
Cancer types: mammary

• Carries the mammary tumor virus locus 2 (Mtv2a) allele, which controls endogenous MMTV expression and hormone-induced tumor development (Golovkina et al. 1996; van Nie and Dux 1971)

• Nearly all breeding females develop tumors before one year; most females have small tumors by first parturition

• MMTV is transmitted through both the milk and the germinal cells of both sexes (foster nursing does not eliminate the virus)

Ovarian

SWXJ9/BmJ

001079
Cancer types: ovarian and testicular

• Malignant granulosa cell (GC) carcinoma are similar to spontaneous juvenile ovarian GC tumors that occur in young girls (Beamer et al. 1985)

• Tumor incidence and progression enhanced by hormone stimulation: 40% incidence of GC tumors at 6-10 weeks with DHEA-induction; metastases to the lungs and liver by 6-8 months (Tennet et al. 1993)

• Tumor susceptibility in SWXJ9/BmJ mice is controlled by an SWR-derived oncogenic allele (Gct1) on chromosome 4 (Beamer et al. 1998)

• Modifier loci on chromosomes 1, 2, 9, 12, 13, and 15, and 2 QTLs on Chr X also contain genes which collaborate during GC carcinogenesis (Dorward et al. 2005)

• SWXJ9/BmJ mice develop testicular teratomas (Stevens and Varnum 1974)

Pancreatic

B6.Cg-Tg(Ela1-TAg*)289Mjt/J

008247
Cancer types: pancreatic adenocarcinomas

• Acinar microadenoma arise as early as 10 weeks (Tevethia et al. 1997)

• Pancreatic adenocarcinoma develop between 15 to 32 weeks with greater than 90% incidence

NOD.Cg-Tg(Ins2-TAg)1Lt Prkdc^scid/DvsJ and NOD/ShiLt-Tg(RipTAg)1Lt/J

002380 and 002033
Cancer types: pancreatic adenomas

• Homozygotes develop pancreatic beta cell adenoma (Hamaguchi et al. 1991; Serreze et al. 1997)

• Produce 2-3 litters before the insulin secreted from the adenoma makes them too hypoglycemic

• Adenomas are free of the autoimmune T cells in 002380, compared to T cells found in the adenomas of the 002033 strain

Prostate Cancer

C57BL/6-Tg(TRAMP)8247Ng/J and (C57BL/6-Tg(TRAMP)8247Ng/J x FVB/NJ)F1/J 

003135 and 008215
Cancer types: prostate

• Progressive prostate cancer with distant site metastases (Greenberg et al. 1995; Albertelli et al. 2006)

  • Disease ranges from mild intraepithelial hyperplasia to multinodular malignant neoplasia, including neuroendocrine tumors and adenocarcinoma

  • Tumors detected in the prostate as early as 10 weeks

• Metastases to the lungs, lymph nodes, and other sites evident by 28 weeks in all aged mice

• Tumor latency is variable and background and hormone dependent

FVB-Tg(C3-1-Tag)cJeg/JegJ

013591
Cancer types: mammary (females) and prostate (males)

• Females develop multiple mammary ductal adenocarcinoma by 6 months (Maroulakou et al. 1994)

• 10% of females mice exhibit lung metastasis at 6 months

• 100% of males develop high grade prostatic intraepithelial neoplasia in ventral prostate at 4-12 months

• 19% of males exhibit carcinoma by 7 months

Skin

DBA/2J

000671
Cancer types: melanoma xenograft

• Subcutaneously transplanted M-3 or Cloudman S91 melanoma cells Useful for testing efficacy of therapeutics – vaccines or drugs Faster tumor growth of Cloudman melanoma cells in thymectomized DBA/2 mice (Nordlund and Askenase. 1983)

• Cimetidine (an H-2 antihistamine), pyrilamine (an H-1 antihistamine), or proxicromil (a mast cell stabilizer) treatment retards tumor growth 
  (Kircheis R et al. 2000)

• Part of our unique Genetic Stability Program the prevents cumulative genetic drift

• Resequenced by the NIEHS-supported Resequencing Project 

• Extensive phenotypic information available from the Mouse Phenome Database

STOCK Ptch1^tm1Mps/J

003081
Cancer types: skin (basal cell carcinoma), brain (medulloblastomas)

• UVB radiation-induced, hair follicle-derived, basal cell carcinomas develop in heterozygotes with 100% incidence (Aszterbaum et al. 1999)

• Some heterozygotes may develop medulloblastoma with age

• As a LacZ reporter strain, it may be used to visualize Ptch1 expression

B6.Cg-Braf^tm1Mmcm Pten^tm1Hwu Tg(Tyr-cre/ERT2)13Bos/BosJ 

013590

Cancer types: melanoma, metastatic melanoma

• Tamoxifen-inducible Braf activating mutation and Pten knockout allele
• Topical application of tamoxifen leads to 100% induction of melanoma within 3-4 weeks, with lung metastases
• Melanoma develops spontaneously in 25% of non-induced mice between 2 and 12 months

Testicular

129T2/SvEmsJ

002065
Cancer types: testicular teratomas

• High incidence of spontaneous testicular teratomas: 30% incidence in this substrain which may be increased by induction (Stevens LC. 1973)

• Early onset (by embryonic day 16); tumors primarily benign

Thyroid

B6(129)-Duox2^thyd/J

005543
Cancer types: thyroid

• Thyroid gland hyperplasia in homozygotes (Johnson et al. 2007)

• Highly proliferating epithelial cells give rise to bilateral thyroid adenoma at one to two months

• Dysplastic anterior pituitary gland develops large abnormal cells harboring multiple nuclei

Uterine

B6.129S4-Cdkn1b^tm1Mlf/J

002781
Cancer types: (induced) uterine, pituitary, intestinal and lung

• Uterine tumors are induced (with 73% incidence) by IP injections of urethane (Fero et al. 1996; Besson et al. 2006)

• Susceptible to radiation- and chemically-induced pituitary, intestine, and lung adenomas

• Lifespan shortened due to benign intermediate lobe pituitary tumors

• Females infertile

Cre-lox conditional alleles

B6.129S2-Trp53^tm1Brn/J

008462
Cancer types: conditional allele

• Exons 2-10 are flanked by loxP sites, in the absence of Cre recombinase mice do not have any phenotype (Jonkers et al. 2001)

• When bred to mice with a Cre recombinase gene under the control of a promoter of interest, expression is deleted in the tissue of interest resulting in tumor development (Clark-Knowles et al. 2007; Kazarian et al. 2009; Adams et al. 2011; Zheng et al. 2008; Uziel et al. 2005)

• Heterozygotes may be bred, homozygotes have a somewhat reduced fertility, but may be bred

B6.129S4-Pten^tm1Hwu/J

006440
Cancer types: conditional allele

• Exon 5 is flanked by loxP sites, in the absence of Cre recombinase mice are viable, fertile, normal in size and do not display any gross physical or behavioral abnormalities (Lesche et al. 2002)

• When bred to mice with a Cre recombinase gene under the control of a promoter of interest, expression is deleted in the tissue of interest resulting in tumor development (Guertin et al. 2009; Lu et al. 2007)

STOCK Bcl2^tm1Irt/J

008882
Cancer types: conditional allele

• Mice have loxP-flanked neo cassette upstream of exon 2, as well as a loxP site downstream of exon 2 (Thorp et al. 2009)

• When bred to mice that express Cre recombinase, resulting offspring can have one of three resulting genotypes in the cre-expressing tissue(s); only the neo selection cassette deleted, only exon 2 deleted, or both the neo selection cassette and exon 2 deleted.

• Cre mediated deletion events that delete exon 2 result in loss of Bcl2 protein, a pro-apoptotic gene