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Guidelines
Suggested parameters and sets of instructions outlining best practices and standards for accomplishing specific animal care and use research duties.

Guidelines on Use of Streptozotocin in Rodents

Unit for Laboratory Animal Medicine

| Approval Date:

January 10, 2025 12:00 am

To provide guidance when using of streptozotocin for induction of diabetes mellitus (DM) in rats and mice.

To describe the appropriate post-injection monitoring of rodents.

Responsibility

  1. Investigators using STZ to induce diabetes in rodents

Glossary Definitions

Streptozotocin (STZ)

An antitumor/antibiotic compound isolated from Streptomyces achromogenes with potent toxicity to beta islet cells of the pancreas.

Carcinogen

An agent capable of causing cancer.

Teratogen

An agent capable of causing developmental abnormalities.

Cytotoxic

Possessing ability to exert toxic effects on a cell.

Background

1. STZ Uses & Properties

  1. Depending on the dose and dose frequency, STZ can be used to induce insulin-dependent Type 1 DM or non-insulin-dependent Type 2 DM.
  2. STZ is known to cause hepatic and renal toxicity in mice and rats. Due to toxic effects and disease progression, some animal mortality can occur. However, steps to reduce mortality must be taken.
  3. STZ is also a carcinogen, teratogen, and has been shown to affect fertility in animal studies.
  4. The effect of STZ on different rodent strains is variable. ULAM recommends starting at the lower end of the dose ranges until performance for a given strain can be established.

2. Common Sequelae in DM Models

  1. Increased appetite, defecation, thirst, and urination.
    1. Ensure appropriate availability of water ensured (e.g., if water bottles are being supplied, consider providing two bottles).
    2. Cage change frequency may need to be increased to account for increased urination.
  2. Kidney injury
  3. Cardiovascular disease
  4. Genitourinary infection
  5. Vision loss

3. Rat Dosages

  1. Recommended doses vary considerably due to strain, age, and weight differences in susceptibility to STZ, as well as variation in the bioactivity of the STZ itself. A general range for use is 42-65 mg/kg administered intraperitoneally (IP).

4. Mouse Dosages

  1. As with rats, strain susceptibility varies considerably and vendor variation may be significant when using outbred stocks. Even variation between vendors has been documented. The dose range of STZ for mice is much higher and wider than rats: 40-200 mg/kg IP.

Procedures for STZ Preparation & Administration

1. Protocol

  1. Procure animals to allow for adequate acclimation time.
  2. The night before the injection, fast all animals to maximize the effectiveness of the STZ. Drinking water must still be provided.
  3. Attain accurate body weights to administer an exact dose. Dose younger, lighter animals the higher end of the dose range compared to older, heavier animals (due to higher metabolic rate in younger animals).
  4.  Prepare STZ using sterile technique immediately prior to injection. Following proper procedures as outlined in Animals Administered a Hazardous Substance Requiring Containment to reduce STZ exposure to personnel.

2. Post-injection Procedures & Monitoring

  1. Hypoglycemia (blood glucose < 40 mg/dL) is expected 8-24 hours after STZ injection.
  2. Provision of sucrose water during the induction period can reduce morbidity and mortality. Upon completion of the injections, provide animals with 10% sucrose water for 48 hours in order to prevent a potentially fatal hypoglycemia.
  3. Test animal blood glucose 48 hours post STZ injection; if they are hyperglycemic at this time, they can be returned to standard drinking water.
  4. Monitor animals daily during the induction period and at least weekly, once the animal has stabilized.
    1. Monitoring is imperative so that deterioration in health can be noted and addressed in a timely manner.
    2. Use the End-Stage Illness Scoring System to assist in determining appropriate endpoints.

References

  1. Deeds MC, Anderson JM, Armstrong AS, Gastineau DA, Hiddinga HJ, Jahangir A, Eberhardt NL, Kudva YC. 2011. Single dose streptozotocin-induced diabetes: considerations for study design in islet transplantation models. Lab Anim. 45(3):131-40
  2. Furman BL. 2021. Streptozotocin-induced diabetic models in mice and rats. Current Protocols, 1, e78. doi: 10.1002/cpz1.78
  3. Graham ML, Janecek JL, Kittredge JA, Hering BJ, Schuurman HJ. 2011. The streptozotocin-induced diabetic nude mouse model: differences between animals from different sources. Comp Med. 61(4):356-60.
  4. Hayashi K, Kojima R, Ito M. 2006. Strain differences in the diabetogenic activity of streptozotocin in mice. Biol Pharm Bull. 29(6):1110-9.
  5. Li RL, Sherbet DP, Elsbernd BL, Goldstein JL, Brown MS, Zhao TJ. 2012. Profound hypoglycemia in starved, ghrelin-deficient mice is caused by decreased gluconeogenesis and reversed by lactate or fatty acids. J Biol Chem.

SPECIES: Mice / Rats

Questions?

Questions or concerns about the content of this document should be directed to the Unit for Laboratory Animal Medicine (ULAM) at (734) 764-0277 or [email protected].