A hypomorphic myogenin allele reveals distinct myogenin expression levels required for viability, skeletal muscle development, and sternum formation

Jay L. Vivian, Lin Gan, Eric N. Olson, William H. Klein

Research output: Contribution to journalArticle

Abstract

The myogenic basic helix-loop-helix transcription factor myogenin plays an essential role in the differentiation of skeletal muscle and, secondarily, in rib and sternum formation during mouse development. However, virtually nothing is known about the quantitative requirements for myogenin in these processes. Here, we describe the generation of mice carrying a hypomorphic allele of myogenin, which expresses myogenin transcripts at approximately one-fourth the level of the wild-type myogenin allele. The hypomorphic allele in combination with wild-type and myogenin-null alleles was used to create an allelic series. Embryos representing the complete range of genotypes from homozygous wild type to homozygous null were analyzed for their viability, ability to form normal ribs and sternum, and extent of skeletal muscle differentiation. Embryos carrying the hypomorphic myogenin allele over a wild-type allele were normal. In embryos bearing homozygous hypomorphic alleles, the sternum developed normally and extensive skeletal muscle differentiation occurred. However, muscle hypoplasia and reduced muscle- specific gene expression were apparent in these embryos, and the mice were not viable as neonates. When the hypomorphic allele was placed over a myogenin-null allele, the resulting embryos had sternum defects resembling homozygous myogenin-null embryos, and there was severe muscle hypoplasia. Our results demonstrate that skeletal muscle formation is highly sensitive to the absolute levels of myogenin and that correct sternum formation, skeletal muscle differentiation, and viability each require distinct threshold levels of myogenin.

Original languageEnglish (US)
Pages (from-to)44-55
Number of pages12
JournalDevelopmental Biology
Volume208
Issue number1
DOIs
StatePublished - Apr 1 1999
Externally publishedYes

Fingerprint

Myogenin
Sternum
Muscle Development
Skeletal Muscle
Alleles
Embryonic Structures
Ribs
Muscles
Basic Helix-Loop-Helix Transcription Factors

Keywords

  • bHLH proteins
  • Muscle-specific gene expression
  • Myogenin
  • Skeletal muscle differentiation

ASJC Scopus subject areas

  • Molecular Biology
  • Developmental Biology
  • Cell Biology

Cite this

A hypomorphic myogenin allele reveals distinct myogenin expression levels required for viability, skeletal muscle development, and sternum formation. / Vivian, Jay L.; Gan, Lin; Olson, Eric N.; Klein, William H.

In: Developmental Biology, Vol. 208, No. 1, 01.04.1999, p. 44-55.

Research output: Contribution to journalArticle

@article{60eac75a320e4b01a63c548aa9b18432,
title = "A hypomorphic myogenin allele reveals distinct myogenin expression levels required for viability, skeletal muscle development, and sternum formation",
abstract = "The myogenic basic helix-loop-helix transcription factor myogenin plays an essential role in the differentiation of skeletal muscle and, secondarily, in rib and sternum formation during mouse development. However, virtually nothing is known about the quantitative requirements for myogenin in these processes. Here, we describe the generation of mice carrying a hypomorphic allele of myogenin, which expresses myogenin transcripts at approximately one-fourth the level of the wild-type myogenin allele. The hypomorphic allele in combination with wild-type and myogenin-null alleles was used to create an allelic series. Embryos representing the complete range of genotypes from homozygous wild type to homozygous null were analyzed for their viability, ability to form normal ribs and sternum, and extent of skeletal muscle differentiation. Embryos carrying the hypomorphic myogenin allele over a wild-type allele were normal. In embryos bearing homozygous hypomorphic alleles, the sternum developed normally and extensive skeletal muscle differentiation occurred. However, muscle hypoplasia and reduced muscle- specific gene expression were apparent in these embryos, and the mice were not viable as neonates. When the hypomorphic allele was placed over a myogenin-null allele, the resulting embryos had sternum defects resembling homozygous myogenin-null embryos, and there was severe muscle hypoplasia. Our results demonstrate that skeletal muscle formation is highly sensitive to the absolute levels of myogenin and that correct sternum formation, skeletal muscle differentiation, and viability each require distinct threshold levels of myogenin.",
keywords = "bHLH proteins, Muscle-specific gene expression, Myogenin, Skeletal muscle differentiation",
author = "Vivian, {Jay L.} and Lin Gan and Olson, {Eric N.} and Klein, {William H.}",
year = "1999",
month = "4",
day = "1",
doi = "10.1006/dbio.1998.9182",
language = "English (US)",
volume = "208",
pages = "44--55",
journal = "Developmental Biology",
issn = "0012-1606",
publisher = "Academic Press Inc.",
number = "1",

}

TY - JOUR

T1 - A hypomorphic myogenin allele reveals distinct myogenin expression levels required for viability, skeletal muscle development, and sternum formation

AU - Vivian, Jay L.

AU - Gan, Lin

AU - Olson, Eric N.

AU - Klein, William H.

PY - 1999/4/1

Y1 - 1999/4/1

N2 - The myogenic basic helix-loop-helix transcription factor myogenin plays an essential role in the differentiation of skeletal muscle and, secondarily, in rib and sternum formation during mouse development. However, virtually nothing is known about the quantitative requirements for myogenin in these processes. Here, we describe the generation of mice carrying a hypomorphic allele of myogenin, which expresses myogenin transcripts at approximately one-fourth the level of the wild-type myogenin allele. The hypomorphic allele in combination with wild-type and myogenin-null alleles was used to create an allelic series. Embryos representing the complete range of genotypes from homozygous wild type to homozygous null were analyzed for their viability, ability to form normal ribs and sternum, and extent of skeletal muscle differentiation. Embryos carrying the hypomorphic myogenin allele over a wild-type allele were normal. In embryos bearing homozygous hypomorphic alleles, the sternum developed normally and extensive skeletal muscle differentiation occurred. However, muscle hypoplasia and reduced muscle- specific gene expression were apparent in these embryos, and the mice were not viable as neonates. When the hypomorphic allele was placed over a myogenin-null allele, the resulting embryos had sternum defects resembling homozygous myogenin-null embryos, and there was severe muscle hypoplasia. Our results demonstrate that skeletal muscle formation is highly sensitive to the absolute levels of myogenin and that correct sternum formation, skeletal muscle differentiation, and viability each require distinct threshold levels of myogenin.

AB - The myogenic basic helix-loop-helix transcription factor myogenin plays an essential role in the differentiation of skeletal muscle and, secondarily, in rib and sternum formation during mouse development. However, virtually nothing is known about the quantitative requirements for myogenin in these processes. Here, we describe the generation of mice carrying a hypomorphic allele of myogenin, which expresses myogenin transcripts at approximately one-fourth the level of the wild-type myogenin allele. The hypomorphic allele in combination with wild-type and myogenin-null alleles was used to create an allelic series. Embryos representing the complete range of genotypes from homozygous wild type to homozygous null were analyzed for their viability, ability to form normal ribs and sternum, and extent of skeletal muscle differentiation. Embryos carrying the hypomorphic myogenin allele over a wild-type allele were normal. In embryos bearing homozygous hypomorphic alleles, the sternum developed normally and extensive skeletal muscle differentiation occurred. However, muscle hypoplasia and reduced muscle- specific gene expression were apparent in these embryos, and the mice were not viable as neonates. When the hypomorphic allele was placed over a myogenin-null allele, the resulting embryos had sternum defects resembling homozygous myogenin-null embryos, and there was severe muscle hypoplasia. Our results demonstrate that skeletal muscle formation is highly sensitive to the absolute levels of myogenin and that correct sternum formation, skeletal muscle differentiation, and viability each require distinct threshold levels of myogenin.

KW - bHLH proteins

KW - Muscle-specific gene expression

KW - Myogenin

KW - Skeletal muscle differentiation

UR - http://www.scopus.com/inward/record.url?scp=0033121066&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0033121066&partnerID=8YFLogxK

U2 - 10.1006/dbio.1998.9182

DO - 10.1006/dbio.1998.9182

M3 - Article

C2 - 10075840

AN - SCOPUS:0033121066

VL - 208

SP - 44

EP - 55

JO - Developmental Biology

JF - Developmental Biology

SN - 0012-1606

IS - 1

ER -