Mouse Strains

B6.Cg-Lepob/J Mouse Strain

By February 6, 2019 July 30th, 2019 No Comments

Overview

B6.Cg-Lepob/J, also known as B6 ob or ob/ob, is a mutant strain of mouse possessing a leptin mutation that confers an obese phenotype.[1]

History

The ob leptin mutation arose spontaneously in a stock of V/Le mice at the Jackson Laboratory in 1949. The current B6 ob strain was then developed by backcrossing these V/Le mice with C57BL/6J for around fifty generations.[1] C57BL/6J is one of the most popular mouse strains and derives from the offspring of a cross carried out by Little in 1921.[2]

Physical Characteristics

B6 ob mice are severely obese, and so have a much greater body weight than wild-type C57BL/6J. They also have enlarged quadricep muscles, increased formation of adipose tissue in the bone marrow, and their hind limbs have lower bone mass than normal. Females have smaller ovaries and uterus than normal.[1]

Behavioral Characteristics & Handling

This strain does not express the hormone leptin, something that has been linked to altered behavior in reward-based experiments. For example, a 2016 study[3] found that B6 ob mice spent longer ingesting cocaine in a cocaine-conditioned reward experiment, and linked this abnormality with deficits in leptin-evoked dopamine signaling.

The mutation has also been associated with analgesia, as shown by decreased responses to harmful thermal stimuli in the hotplate test and tail-flick. The effect on tail-flick results became more pronounced with age.[4]

Obese strains such as B6 ob should generally be avoided for paradigms requiring a large degree of physical exertion such as the rotarod, forced swim test, and Morris water maze.

No information on the handling of this strain could be found. Researchers requiring a more docile strain may want to avoid B6 ob as a precautionary measure.

Health Characteristics

As mentioned above, B6 ob mice do not express the peptide hormone leptin, as their leptin gene has a nonsense mutation (a point mutation changing a cytosine to a thymine). In homozygotes, this confers a severely obese phenotype, accompanied by a number of other serious abnormalities.

These mice eat much more than the wild-type strain and gain weight rapidly, reaching a noticeable supernormal weight by one month of age, and reaching up to three times the weight of a wild-type B6 mouse. Adipocyte numbers are elevated. Even when their diet is restricted to the normal intake for a B6 mouse, they continue to deposit excess fat and gain weight.

Their weight gain engenders a variety of metabolic symptoms, including type two diabetes, characterized by elevated levels of insulin, blood sugar, as well as pituitary and adrenal hormones. They become insulin resistant, glucose intolerant, hypothermic, and show deficits in wound healing.

On the C57BL/6J background, the hyperglycemia is only transient, ending by around 14 to 16 weeks of age. Transplantation of healthy adipose tissue and injection of recombinant leptin greatly mitigate their disease symptoms.

Fertility is severely reduced in both males and females. In females, the reduction in the size of the ovaries leads to hypercytolipidemia in the endometrial epithelial tissue layers and follicular granulosa, as well as decreased ovarian hormone production.[1]

Major Experimental Uses

The obese and diabetic phenotype of B6 ob mice makes them especially useful in the study of type 2 diabetes, metabolism, and endocrine defects. They are also of interest to researchers looking into wound healing, defects in adipose, fertility, and pancreatic function, as well as immunology.[1]

References

  1. 000632 – B6.Cg-Lep/J. 2018. 000632 – B6.Cg-Lep/J. [ONLINE] Available at: https://www.jax.org/strain/000632. [Accessed 27 November 2018].
  2. MGI – Inbred Strains: C57BL. 2018. MGI – Inbred Strains: C57BL. [ONLINE] Available at: http://www.informatics.jax.org/inbred_strains/mouse/docs/C57BL.shtml. [Accessed 12 November 2018].
  3. Shen, M, Jiang, C, Liu, P and Ma, L. Mesolimbic leptin signaling negatively regulates cocaine-conditioned reward. Translational Psychiatry. volume 6, page e972. 2016.
  4. Rodgers HM, Liban S, Wilson LM. Attenuated pain response of obese mice (B6.Cg-lep(ob)) is affected by aging and leptin but not sex. Physiol Behav. 2014. Jan 17;123:80-5.

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