Harlan Teklad动物饲料Tamoxifen Diets

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Harlan Teklad动物饲料Tamoxifen Diets

Diets with tamoxifen activate CreER

Several references cite use of tamoxifen-containing diets for models with Cre under the control of a mutated estrogen receptor. Inotiv Teklad diets makes a variety of tamoxifen-containing diets customized to meet your research needs. We also make a variety of doxycycline-containing diets for tet regulated systems. If you have any questions, don’t hesitate to consult a nutritionist.

Teklad stocks tamoxifen and tamoxifen citrate

Tamoxifen is most often added to the diet as a tamoxifen-sucrose mixture. The options below are made frequently and often available for quicker shipment.

Tamoxifen containing diets can be further customized with use of different base diets, adjustment of sucrose (or other palatant) levels, tamoxifen dose, or food color.

Teklad offers diet with USP grade tamoxifen and tamoxifen citrate

Tamoxifen
mg per kg diet
Daily tamoxifen
mg per kg body weight1
Diet code Diet code
Natural colored Red
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 three-four g intake
2 Tamoxifen citrate is 66% tamoxifen
3 Referred to as TAM400/CreER in Europe (TD.55125 )

Please add 10 day lead time for irradiated diets; minimum 3 kg orders are required for stocked and customized items.

These diets all have tamoxifen premixed with ~five percent sucrose as a palatability enhancer; however, feed aversion may still occur. If intake is a problem, see below for advice.

Teklad Global 2016 — base diet in these examples — is only one of several minimal phytoestrogen diets Teklad produces. Consult a nutritionist about use of other base diets.

Key planning information

  • Minimum order quantity is three kg, sufficient for feeding ~20 mice for one month
  • Store diet refrigerated and plan to use within six months
  • Typical lead time is two weeks (four weeks if irradiated)
  • Irradiation (optional) minimal dose of 20 kGy (Must be requested at time of order)
  • To place an order: contact Teklad Customer Service at 800.483.5523 or initiate order online

Mice need time to adjust

Plan for:

  • Initial reduction in food intake and weight loss
  • Daily observation of animal tolerance — consult your IACUC for monitoring metrics
  • Intervene when necessary

Other researchers have the following advice

If intake seems to be a problem:

  • Determine if a lower dose is effective for your model by conducting a tamoxifen dose feeding trial
  • 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

Safe handling of 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.

Key points from literature

  • Length of treatment varies from one to two weeks1,2,5,6,7,8 to one to two months3,4,8
  • Pure tamoxifen1,5,8 and tamoxifen citrate1,2,3,4,6,7 are both effective
    Usual tamoxifen doses are ~40-80 mg per kg body weight per day
  • Typical inclusion for pure tamoxifen is 250 mg8 or 500 mg1,5 and for tamoxifen citrate is 400 mg per kg diet1,2,3,4,6,7
  • Initial weight loss of ten % is reported1,2,4,7,8, associated with reduced food intake2
  • Subsequent recovery of body weight after returning to regular diet may be compromised by gene inactivation2,7

Selected tamoxifen 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 Kardakaris R, Gareus R, Xanthoulea S, Pasparakis M. 2011. Endothelial and macrophage-specific deficiency of P38alpha MAPK does not affect the pathogenesis of atherosclerosis in ApoE-/- mice. PLoS One 6:e21055.

4 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.

5 Koitabashi N, Bedja D, Zaiman AL, Pinto YM, Zhang M, Gabrielson KL, Takimoto E, Kass DA. 2009. Avoidance of transient cardiomyopathy in cardiomyocyte-targeted tamoxifen-induced MerCreMer gene deletion models. Circ Res 105:12-15.

6 Kratsios P, Catela C, Salimova E, Huth M, Berno V, Rosenthal N, Mourkioti F. 2009. Distinct roles for cell-autonomous Notch signaling in cardiomyocytes of the embryonic and adult heart. PCirc Res 106:559-572.

7 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.

8 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.

If you have any questions regarding tamoxifen diets, please don’t hesitate to contact a nutritionist at askanutritionist@inotivco.com.