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Inotiv Teklad Diets with tamoxifen activate CreER

Tamoxifen-containing custom diets are widely used for models with Cre under the control of a mutated estrogen receptor [Tamoxifen diet references ]. Inotiv Teklad diets makes a variety of tamoxifen-containing diets customized to meet your research needs.

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Teklad offers diet with USP grade tamoxifen and tamoxifen citrate

Tamoxifen
mg per kg diet
Daily tamoxifen
mg per kg body weight1
Diet code
(Natural Colored)
Diet code
(Red Colored)
250 40 TD.130855 TD.130856
500 80 TD.130857 TD.130858
400 citrate2 40 TD.130859 TD.130860 3

1 Assumes 20-25 g body weight and 3-4 g intake
2 Tamoxifen citrate is 66% tamoxifen
3 Referred to as TAM400/CreER in Europe (TD.55125 )

Tamoxifen is most often added to the diet as a tamoxifen-sucrose mixture to aid in the distribution of tamoxifen within the diet. Anecdotal reports suggest sucrose or other sweeteners such as molasses may function as palatability enhancers and improve intake. If intake is noticeably reduced, see “Researcher's advice” for additional feeding strategies.

Further customization of tamoxifen diets

Tamoxifen containing diets can be further customized utilizing different base diets, adjustment of sucrose levels, tamoxifen dose, or food color. In the above examples, Teklad Global 2016 is a type of chow diet, and one of several minimal phytoestrogen diets in the Teklad diet line. Opting for Teklad Global 2019 as the base diet will increase protein, fat, and energy levels, which may prove beneficial during reduced intake. The selections in the table above are commonly chosen and available for quicker shipment. Contact one of our expert nutritionists regarding the use of other base diets.

Planning

 Key planning information

  • Minimum order quantity is 3 kg, sufficient for feeding ~20 mice for one month.
  • TD.130855-TD.130860 are available for quick shipment if irradiation is not needed. The typical lead time for other tamoxifen containing diets is two weeks (four weeks if irradiated).
  • Irradiation must be requested at time of order.
  • To place an order: contact Teklad Customer Service at 800.483.5523, tekladorders@inotiv.com, or initiate an order online.

Diet Adjustment

Mice need time to adjust

Plan for:

  • Initial weight loss of 10% is reported1,2,3,4,5, associated with reduced food intake2 
  • Daily observation of animal tolerance — consult your IACUC for monitoring metrics
  • Intervene when necessary

References:

1 Andersson KB, Winer LH, Mork HK, Molkentin JD, Jaisser F. 2010. Tamoxifen administration routes and dosage for inducible Cre-mediated gene disruption in mouse hearts. Transgenic Res 19:715-725.

2 Chiang PM, Ling J, Jeong YH, Price DL, Aja SM, Wong PC. 2010. Deletion of TDP-43 down-regulates Tbc1d1, a gene linked to obesity, and alters body fat metabolism. Proc Natl Acad Sci USA 107:16320-16324.

3 Kiermayer C, Conrad M, Schneider M, Schmidt J, Brielmeier M. 2007. Optimization of spatiotemporal gene inactivation in mouse heart by oral application of tamoxifen citrate. Genesis 45:11-16.

4 Miro-Murillo M, Elorza A, Soro-Arnaiz I, Albacete-Albacete L, Ordonez A, Balsa E, Vara-Vega A, Vazquez S, Fuertes E, Fernandez-Criado C, Landazuri MO, Aragones J. 2011. Acute Vhl gene inactivation induces cardiac HIF-dependent erythropoietin gene expression. PLoS One 6:e22589.

5 Welle S, Burgess K, Thornton CA, Tawil R. 2009. Relation between extent of myostatin depletion and muscle growth in mature mice. Am J Physiol Endocrinol Metab.Oct;297(4):E935-40.

Researcher's Advice

Other researchers have offered the following advice.

If intake seems to be a problem:

  • Gradually acclimate mice by mixing tamoxifen-containing pellets with regular feed pellets
  • Wet the food, then place in a dish inside the cage (requires daily replacement)
  • Feed tamoxifen diet on weekdays, regular diet on weekends
  • Alternate weeks (two weeks on tamoxifen diet, one week off) for longer treatments
  • Determine if a lower dose is effective for your model

Safe Handling

Safely managing tamoxifen diets

  • Tamoxifen is a selective estrogen receptor modulator (SERM) meaning it can repress actions of estrogen or have pro-estrogen effects.
  • Usual dose for therapeutic effects in humans is 20 mg/day. Tamoxifen diets for rodents typically contain ~one to two mg/pellet.
  • Accidental tamoxifen exposure can be minimized by using typical lab precautions of lab coat, gloves, and mask when handling the diet.
  • Your chemical safety department should be contacted for additional institution specific guidelines for handling and disposal of tamoxifen containing diets.

Literature

Key points from literature

    • Tamoxifen diets are used to induce recombination in a variety of tissues and cell types for both functional gene expression modulation as well as lineage tracing experiments.
    • Typical inclusion for pure tamoxifen is 250 mg or 500 mg per kg diet and for tamoxifen citrate is 400 mg per kg diet. This corresponds to ~40 and ~80 mg/kg body weight assuming 20-25 g body weight and intake of 3-4 g/day.
      • As food intake is reduced, dose will also be reduced.
      • There do not appear to be any differences in efficacy or tolerability between tamoxifen and tamoxifen citrate when absolute tamoxifen concentration is equal.
    • The reported length of feeding varies from 1 day to up to 18 weeks 
      • The 500 mg tamoxifen/kg diet dose is typically used for 4 weeks or less.
    • The age at which dietary tamoxifen has been initiated varies from as soon as weaning has occurred to well into the adult stage.
    • Most of the references utilize one of the one of the stocked tamoxifen diets (TD.130855-TD.130860). However, TD.170935 is a modification of the 60% kcal from fat diet TD.06414 to include 400 ppm tamoxifen citrate. Tamoxifen can be included in virtually any diet; consult a nutritionist about inclusion in other custom diets.

If you have any questions regarding tamoxifen diets, please don’t hesitate to contact a nutritionist.

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