Influence Of Genotype On Muscle Regeneration In Mice
Paul Pietsch (Introduced by M. B. Chenoweth)
Biochemical Research Laboratory, The Dow Chemical Co., Midland, Michigan *
From Proceedings of the Society for Experimental Biology and Medicine, vol.
117: 927-928, 1964.
Web Contact: pietsch@indiana.edu
Summary
Regeneration was studied in muscles of mice of 4 genetic types. It was learned
that the number of new fibers differed with varying genotype. A hybrid strain
exhibited regeneration a levels intermediate between those observed among
muscles of the parent type.
Skeletal muscle is one of the regenerative tissues in mammals (1-4). In the
past few years in particular a body of evidence has emerged from several
independent laboratories indicating that the primary events are essentially the
same as those that operated in the differentiation of muscle in the embryo
(2-4). It seemed quite possible that the amount of regeneration in muscle
would show a relationship to pedigree. The specific objective of this work was
to find out if genetically different strains of mice would exhibit different
levels of regeneration.
Materials and Methods
Experiments were performed with male Jackson Memorial Laboratory mice
approximately 3 months of age, from one of the following strains: B6AF-1,
SLJ/J, C57BL/6J and A/J (5). Strains C57BL/6J and A/J are purebreds. Strain
B6AF-1 is a hybrid from matings between C57BL/6J females and A/J males. Strain
SLJ/J is an independent line of Swiss Webster mouse. At the time of
experimentation animals weighed 23-25 g.
Mice were anesthetized light with methoxyflurane and 1 mm x 1 mm transections
were made in their left tibialis anterior muscles. Wounds were inflicted
between 9:35 and 10:35 a.m. Regeneration was allowed to proceed for 5 days
(+/- 15 minutes) at which time animals were killed and wound areas excised and
fixed in Bouin's fluid. Serial sections were cut tangential to the superficial
surface of the muscle and were stained with hematoxylin-eosin.
Results
Histological examination of serial sections through wounds revealed large
numbers of differentiating muscle fibers in virtually all sections from animals
of strains B6AF-1, C57BL/6J and SLJ/J. In wounds from the A/J series,
regeneration, while evident, was appreciably reduced as compared with the
other strains. However, the newly developing fibers in the A/J series were,
individually, typical for this post-operative time.
Counts were made of regenerating muscle fibers from 10 or more randomly
selected sections of at least 3 specimens in each strain. The values,
expressed as a ration of new fibers to injured fibers, are summarized in Table
I. Swiss mice (SJL/J) showed the best regeneration of the four strains tested.
Strains C57BL/6J and A/J exhibited, respectively, 2.01 and 0.645 regenerating
muscle fibers per injured one. Values for hybrids of the latter strains
(B6AF-1) averaged 1.29. Interestingly, this is very close to the mean between
the parental types (1.32).
Table I. Regeneration in Muscle from Mice of Different Genotype as Judged by the Ratio of Regenerating to Injured Fibers**
| STRAIN | Mean Ratio | Standard Deviation
+/- |
| B6AF-1 | 1.29 | 0.69 |
| SJL/J | 2.10 | 1.23 |
| C57BL/6J | 2.01 | 1.40 |
| A/J | 0.645 | 0.39 |
| **Counts in 10 or more randomly selected sections of 3 or more animals per strain. |
Discussion
As predicted in the introduction, there are pedigree-related differences among
strains of animals with respect to the regeneration of skeletal muscle. The
capacity to regenerate muscle is much less in the A/J stains than in animals of
the other strains tested, to the extent that differences were evident even
without counting fibers. Strains of mice were selected ad hoc. Luckily, a
hybrid was chosen with parental genotypes, one of which is excellent in
regeneration of muscle and the other relatively poor. That the hybird showed
levels of regeneration intermediate between the 2 parental types indicates that
the amount of new muscle produced is governed by multiple, complementary
alleles.
Aside from theoretical considerations, the data indicate the importance of
pedigree selection in experiments involving muscle regeneration where the mouse
is to be the organism of study.
References
- Fields, E. J., Structure and Function of Muscle, G. H. Bourne, Ed., vol.
III, 139, Academic Press, New York and London, 1960
- Lash, J., Holtzer, H., Swift, H., Anat. Rec. 1957, vol. 28, 679.
- Bintliff, S., Walker, B. E., Am J. Anat., 1960, vol. 106, 233
- Pietsch, P., Anat. Rec., 1961, vol. 139, 167
- Handbook on Genetically Standardized JAX Mice, Bar Harbor Times, Bar
Harbor, 1962.
Received September 17, 1964.
*At Indiana University, Bloomington, Indiana, USA since 1970
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pietsch@indiana.edu