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Allelic variants between mouse substrains BALB/cJ and BALB/cByJ influence mononuclear cardiomyocyte composition and cardiomyocyte nuclear ploidy. Sci Rep 2020 05 05;10(1):7605

Date

05/07/2020

Pubmed ID

32371981

Pubmed Central ID

PMC7200697

DOI

10.1038/s41598-020-64621-0

Abstract

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 HM

Author

Michaela Patterson PhD Assistant Professor in the Cell Biology, Neurobiology and Anatomy department at Medical College of Wisconsin




MESH terms used to index this publication - Major topics in bold

Alleles
Animals
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