Allelic variants between mouse substrains BALB/cJ and BALB/cByJ influence mononuclear cardiomyocyte composition and cardiomyocyte nuclear ploidy. Sci Rep 2020 May 05;10(1):7605
Date
05/07/2020Pubmed ID
32371981Pubmed Central ID
PMC7200697DOI
10.1038/s41598-020-64621-0Scopus ID
2-s2.0-85084327709 (requires institutional sign-in at Scopus site) 7 CitationsAbstract
Most mouse cardiomyocytes (CMs) become multinucleated shortly after birth via endoreplication and interrupted mitosis, which persists through adulthood. The very closely related inbred mouse strains BALB/cJ and BALB/cByJ differ substantially (6.6% vs. 14.3%) in adult mononuclear CM level. This difference is the likely outcome of a single X-linked polymorphic gene that functions in a CM-nonautonomous manner, and for which the BALB/cByJ allele is recessive to that of BALB/cJ. From whole exome sequence we identified two new X-linked protein coding variants that arose de novo in BALB/cByJ, in the genes Gdi1 (R276C) and Irs4 (L683F), but show that neither affects mononuclear CM level individually. No BALB/cJ-specific X-linked protein coding variants were found, implicating instead a variant that influences gene expression rather than encoded protein function. A substantially higher percentage of mononuclear CMs in BALB/cByJ are tetraploid (66.7% vs. 37.6% in BALB/cJ), such that the overall level of mononuclear diploid CMs between the two strains is similar. The difference in nuclear ploidy is the likely result of an autosomal polymorphism, for which the BALB/cByJ allele is recessive to that of BALB/cJ. The X-linked and autosomal genes independently influence mitosis such that their phenotypic consequences can be combined or segregated by appropriate breeding, implying distinct functions in karyokinesis and cytokinesis.
Author List
Gan P, Patterson M, Watanabe H, Wang K, Edmonds RA, Reinholdt LG, Sucov HMAuthor
Michaela Patterson PhD Assistant Professor in the Cell Biology, Neurobiology and Anatomy department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
AllelesAnimals
Cell Nucleus
Female
Guanine Nucleotide Dissociation Inhibitors
Insulin Receptor Substrate Proteins
Male
Mice
Mice, Inbred BALB C
Mutation
Myocytes, Cardiac
Ploidies
Sequence Analysis, DNA
Species Specificity
