Mouse Strains

D2.B10-Dmdmdx/J Mouse Strain

By May 24, 2019 October 15th, 2019 No Comments

Overview

D2.B10-Dmdmdx/J, also known as D2-mdx, is a mutant strain of mouse that serves as a model for muscular dystrophy.[1]

History

D2-mdx is originally descended from the commonly used C57BL/6J strain, via the variant C57BL/10ScSn-Dmdmdx/J.[1] The mutation conferring muscular dystrophy arose spontaneously in C57BL/10ScSn-Dmdmdx/J in 1977, and a stock of these mutant mice was taken to the Jackson Laboratory in 1984.[2]

D2-mdx was created by backcrossing C57BL/10ScSn-Dmdmdx/J with normal DBA/2J in 2010.[1] The DBA family is the oldest of all inbred mouse strains, with DBA/2 established by Little in 1930.[3]

Physical Characteristics

D2-mdx appears larger than a normal DBA/2J mouse due to fat accumulation, and it has reduced muscle mass in the hindlimbs. Its fur is light brown, like that of DBA/2J.[1]

Behavioral Characteristics & Handling

As a result of their disease phenotype (see Health Characteristics below) D2-mdx mice perform poorly in the grip strength test, as well as on the rotarod and in the open field test.[4][5] In general, these mice are not especially suitable for experiments involving motor testing, except as a dystrophy model or negative control.

Given the weakness of these mice and their subsequent difficulty moving around and supporting themselves, it is advised that researchers handle them with greater than usual care so as to avoid injury.

Health Characteristics

D2-mdx exhibits a disease phenotype resembling muscular dystrophy in humans. The disease is conferred by a point mutation in the gene Dmd, coding for the protein dystrophin, resulting in a premature stop codon and a truncated protein. The gene is on the X chromosome, and so males of this strain are more strongly affected.[1]

Dystrophin is an extracellular matrix protein which connects the cytoskeleton of a muscle cell to proteins outside the cell. This provides structural rigidity, increasing the overall strength of muscle fibers. When dystrophin is non-functional, muscles are weakened, and the disruption of signaling between muscle cells leads to cell death.

Hence D2-mdx mice show muscle necrosis and fibrosis, loss of muscle fibers, lower muscle weight, inability to regenerate lost fibers, extreme weakness of muscles, and the accumulation of fat. Unlike C57BL/10-mdx mice, this strain does not have an increased incidence of muscle tumors.[1]

Major Experimental Uses

This strain is considered a superior model of human muscular dystrophy than the similar C57BL/10-mdx, as it exhibits more of the characteristic symptoms and its phenotype is more severe overall. Its main use is in muscular dystrophy research and other research on muscular disorders. It is also indicated for research into sensory and neurological disorders.[1][5]

References

  1. 013141 – D2.B10-Dmd/J. 2019. 013141 – D2.B10-Dmd/J. [ONLINE] Available at: https://www.jax.org/strain/013141. [Accessed 28 April 2019].
  2. 001801 – C57BL/10ScSn-Dmd/J. 2019. 001801 – C57BL/10ScSn-Dmd/J. [ONLINE] Available at: https://www.jax.org/strain/01801. [Accessed 28 April 2019].
  3. 000671 – DBA/2J. 2019. 000671 – DBA/2J. [ONLINE] Available at: https://www.jax.org/strain/000671. [Accessed 28 April 2019].
  4. Coley, W. D., Bogdanik, L., Vila, M. C., Yu, Q., Van Der Meulen, J. H., Rayavarapu, S., … Nagaraju, K. 2015. Effect of genetic background on the dystrophic phenotype in mdx mice. Human molecular genetics, 25(1), 130–14.
  5. The Jackson Laboratory. 2019. Muscular Dystrophy Efficacy Studies. [ONLINE] Available at: https://www.jax.org/jax-mice-and-services/in-vivo-pharmacology/neurobiology-services/muscular-dystrophy-efficacy-studies. [Accessed 28 April 2019].

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