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.

Details

Title
Allelic variants between mouse substrains BALB/cJ and BALB/cByJ influence mononuclear cardiomyocyte composition and cardiomyocyte nuclear ploidy
Author
Gan Peiheng 1 ; Patterson, Michaela 2 ; Watanabe, Hirofumi 3 ; Wang, Kristy 3 ; Edmonds, Reilly A 4 ; Reinholdt, Laura G 5 ; Sucov, Henry M 6 

 Department of Regenerative Medicine and Cell Biology, Medical University of South Carolina, Charleston, USA (GRID:grid.259828.c) (ISNI:0000 0001 2189 3475); Department of Stem Cell Biology and Regenerative Medicine, University of Southern California Keck School of Medicine, Los Angeles, USA (GRID:grid.42505.36) (ISNI:0000 0001 2156 6853) 
 Department of Cell Biology, Neurobiology and Anatomy, and Cardiovascular Center, Medical College of Wisconsin, Milwaukee, USA (GRID:grid.30760.32) (ISNI:0000 0001 2111 8460) 
 Department of Regenerative Medicine and Cell Biology, Medical University of South Carolina, Charleston, USA (GRID:grid.259828.c) (ISNI:0000 0001 2189 3475) 
 Department of Stem Cell Biology and Regenerative Medicine, University of Southern California Keck School of Medicine, Los Angeles, USA (GRID:grid.42505.36) (ISNI:0000 0001 2156 6853) 
 The Jackson Laboratory for Mammalian Genetics, Bar Harbor, USA (GRID:grid.249880.f) (ISNI:0000 0004 0374 0039) 
 Department of Regenerative Medicine and Cell Biology, Medical University of South Carolina, Charleston, USA (GRID:grid.259828.c) (ISNI:0000 0001 2189 3475); Department of Medicine, Division of Cardiology, Medical University of South Carolina, Charleston, USA (GRID:grid.259828.c) (ISNI:0000 0001 2189 3475) 
Publication year
2020
Publication date
2020
Publisher
Nature Publishing Group
e-ISSN
20452322
Source type
Scholarly Journal
Language of publication
English
ProQuest document ID
2398582679
Copyright
© The Author(s) 2020. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.