Allelic variants between mouse substrains BALB/cJ and BALB/cByJ influence mononuclear cardiomyocyte composition and cardiomyocyte nuclear ploidy.
Journal
Scientific reports
ISSN: 2045-2322
Titre abrégé: Sci Rep
Pays: England
ID NLM: 101563288
Informations de publication
Date de publication:
05 05 2020
05 05 2020
Historique:
received:
18
01
2020
accepted:
15
04
2020
entrez:
7
5
2020
pubmed:
7
5
2020
medline:
1
12
2020
Statut:
epublish
Résumé
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.
Identifiants
pubmed: 32371981
doi: 10.1038/s41598-020-64621-0
pii: 10.1038/s41598-020-64621-0
pmc: PMC7200697
doi:
Substances chimiques
GDP dissociation inhibitor 1
0
Guanine Nucleotide Dissociation Inhibitors
0
Insulin Receptor Substrate Proteins
0
Irs4 protein, mouse
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
7605Subventions
Organisme : NHLBI NIH HHS
ID : R01 HL070123
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL144938
Pays : United States
Organisme : NIH HHS
ID : R24 OD021325
Pays : United States
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