All animal studies were conducted under protocol 2016–1143 approved by the Georgetown University Animal Care and Use Committee in accordance with NIH guidelines for the ethical treatment of animals. MMTV-NeuT mice [46 (link)] were obtained from Jackson Labs (FVB-Tg(MMTV-Erbb2)NK1Mul/J), and exhibit 100% penetrance of mammary tumorigenesis by 6–7 months [47 (link)]. FAT-ATTAC mice on a C57BL/6 background were kindly provided by Dr. Philipp Scherer, University of Texas Southwestern [28 (link), 48 (link)]. Mice were crossed into the FVB strain for four generations before crossing with MMTV-NeuT mice to produce NeuT/ATTAC mice. A schematic of the breeding is shown in Figure 1A .
Fvb tg mmtv erbb2 nk1mul j
Manufactured by Jackson ImmunoResearch
Sourced in United States
FVB-Tg(MMTV-Erbb2)NK1Mul/J is a transgenic mouse model that expresses the Erbb2 gene under the control of the mouse mammary tumor virus (MMTV) promoter. The model is on an FVB/N genetic background.
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Lab products found in correlation
Lapatinib, by Cayman Chemical (2 mentions)
Clone jc63, by Cayman Chemical (2 mentions)
Tg mmtv cre 4mam j, by Jackson ImmunoResearch (2 mentions)
Nod cg prkdcscid il2rgtm1wjl szj, by Jackson ImmunoResearch (2 mentions)
Lapatinib, by LC Laboratories (2 mentions)
Matrigel matrix, by Corning (2 mentions)
6 protocols using fvb tg mmtv erbb2 nk1mul j
1
Mammary Tumor Mouse Model Development
2
Transgenic Mice for Immunotherapy Research
3
Inducing Fibrosis and Immune Checkpoint Blockade
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MMTV-NeuT mice [36 (link)] were obtained from Jackson Labs (FVB-Tg(MMTV-Erbb2)NK1Mul/J) [37 (link)] and FAT-ATTAC mice on a C57BL/6 background were kindly provided by Dr. Philipp Scherer, University of Texas Southwestern [38 (link), 39 (link)]. FAT-ATTAC mice were crossed into the FVB strain and subsequently with MMTV-NeuT mice to produce NeuT/ATTAC mice as previously described [21 (link)]. In brief, NeuT/ATTAC mice at 6 weeks of age were injected i.p. triweekly with 0.4 mg/kg AP20187 throughout tumor development to induce fibrosis [21 (link)]. At 8 weeks of age, mice were injected i.p. twice weekly with 100 μg of the anti-PD-1 monoclonal antibody (mAb) or a matching isotype-specific IgG mAb for four months. This dose achieved a plasma level of 36 ± 3.6 μg/ml (mean ± S.E., N = 21), suggesting even distribution in total blood volume (unpublished results). All treatments and tumor measurements were carried out by Carlos Benitez and Maria Idalia Cruz under the auspices of the Animal Shared Resource.
4
Modeling MMTV-neu Breast Cancer
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MMTV-neu (FVB-Tg(MMTV-Erbb2)NK1Mul/J; RRID:IMSR_JAX:005038), MMTV-Cre (Tg(MMTV-cre)4Mam/J) and NSG mice (NOD.Cg-PrkdcscidIl2rgtm1Wjl/SzJ; RRID:IMSR_JAX:005557) were obtained from The Jackson Laboratory. CD36flox/flox mice were described previously (Nagendran et al., 2013 (link)). All animal studies were performed in accordance with protocols approved by the Institutional Animal Care and Use Committee (IACUC) at Dartmouth College and Kent State University. Female MMTV-neu mice were treated with 100 mg/kg lapatinib (LC Laboratories; Cat# 388082–77-7) or DMSO by oral gavage BID once a palpable tumor ~100mm3 was discovered (~1 year old). Tumor growth was monitored by caliper measurement every 3 days. Mice were sacrificed when reaching maximum tumor volume permitted by IACUC protocols. For xenograft studies, 1 × 107 BT474 or rBT474 cells resuspended in Matrigel Matrix (Corning; Cat# 354234) were implanted in the mammary fat pad of 6-week old female NSG mice. Upon reaching 300mm3, mice were randomly assigned to one of four treatment groups. Mice were treated with 100 mg/kg lapatinib or DMSO by oral gavage BID in combination with 10 μg anti-CD36 function blocking antibody (Clone JC63.1; Cayman Chemical; Cat# 188150; RRID:AB_10077812) or anti-mouse IgA-isotype control (Abcam; Cat# ab37322).
5
Generating ERBB2; Ptk6-/- Transgenic Mice
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Ptk6 null mice (B6-Ptk6tm1Aty) in the C57BL/6 strain19 (link) were backcrossed with the FVB/N inbred strain (Harlan Laboratories, Frederick, MD, USA) for at least eight generations to generate Ptk6 null mice in FVB/N background. FVB-Ptk6tm1Aty were then crossed with FVB-MMTV-ERBB2 transgenic mice48 (link) (Jackson Laboratories, Bar Harbor, ME, USA, Stock number 005038, FVB-Tg(MMTV-Erbb2)NK1Mul/J) to produce ERBB2;Ptk6−/− animals. These mice carry activated rat c-Neu (Erbb2) (Val664 to Glu664) under the control of the MMTV long-terminal repeat (LTR).
Tissues from age-matched female mice were used in all experiments, and FVB/NJ nontransgenic mice were used for maintaining the lines and nontransgenic controls. Animals were palpated one or two times a week for subcutaneous mass from the age of 8 weeks.
Tissues from age-matched female mice were used in all experiments, and FVB/NJ nontransgenic mice were used for maintaining the lines and nontransgenic controls. Animals were palpated one or two times a week for subcutaneous mass from the age of 8 weeks.
6
Modeling MMTV-neu Breast Cancer
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