Abstract
Two types of mutant allele, one leaky and one null, have been generated by gene targeting at the N-myc locus in embryonic stem cells and the phenotypes of mice homozygous for these mutations have been described. These mutations have shown that N-myc has a number of functions during development, including a role in branching morphogenesis in the lung, which manifests itself at birth in mice homozygous for the leaky allele, and roles in the development of the mesonephric tubules, the neuroepithelium, the sensory ganglia, the gut and the heart, which become evident at midgestation in embryos homozygous for the null allele. In an attempt to define roles for N-myc at other stages of development, we have combined the two types of N-myc mutant allele in a compound heterozygote that as a result contains approximately 15% of normal levels of N-Myc protein. Compound heterozygotes died during gestation at a time intermediate to the times of death of embryos homozygous for either mutation individually, and their death appeared to result from cardiac failure stemming from hypoplasia of the compact subepicardial layer of the myocardium. Investigation of the expression pattern of N-myc and various markers of differentiation in wild-type and compound heterozygote mutant hearts has suggested that N-myc may function in maintaining the proliferation and/or preventing the differentiation of compact layer myocytes. This study illustrates the importance of generating different mutations at a given locus to elucidate fully the function of a particular gene during development.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 485-499 |
| Number of pages | 15 |
| Journal | Development |
| Volume | 119 |
| Issue number | 2 |
| State | Published - Oct 1993 |
Fingerprint
Keywords
- Heart development
- Mouse mutant
- N-myc
- Targeted mutagenesis
ASJC Scopus subject areas
- Cell Biology
- Anatomy
Cite this
Defects in heart and lung development in compound heterozygotes for two different targeted mutations at the N-myc locus. / Moens, Cecilia B.; Stanton, Brian R.; Parada, Luis F.; Rossant, Janet.
In: Development, Vol. 119, No. 2, 10.1993, p. 485-499.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Defects in heart and lung development in compound heterozygotes for two different targeted mutations at the N-myc locus
AU - Moens, Cecilia B.
AU - Stanton, Brian R.
AU - Parada, Luis F.
AU - Rossant, Janet
PY - 1993/10
Y1 - 1993/10
N2 - Two types of mutant allele, one leaky and one null, have been generated by gene targeting at the N-myc locus in embryonic stem cells and the phenotypes of mice homozygous for these mutations have been described. These mutations have shown that N-myc has a number of functions during development, including a role in branching morphogenesis in the lung, which manifests itself at birth in mice homozygous for the leaky allele, and roles in the development of the mesonephric tubules, the neuroepithelium, the sensory ganglia, the gut and the heart, which become evident at midgestation in embryos homozygous for the null allele. In an attempt to define roles for N-myc at other stages of development, we have combined the two types of N-myc mutant allele in a compound heterozygote that as a result contains approximately 15% of normal levels of N-Myc protein. Compound heterozygotes died during gestation at a time intermediate to the times of death of embryos homozygous for either mutation individually, and their death appeared to result from cardiac failure stemming from hypoplasia of the compact subepicardial layer of the myocardium. Investigation of the expression pattern of N-myc and various markers of differentiation in wild-type and compound heterozygote mutant hearts has suggested that N-myc may function in maintaining the proliferation and/or preventing the differentiation of compact layer myocytes. This study illustrates the importance of generating different mutations at a given locus to elucidate fully the function of a particular gene during development.
AB - Two types of mutant allele, one leaky and one null, have been generated by gene targeting at the N-myc locus in embryonic stem cells and the phenotypes of mice homozygous for these mutations have been described. These mutations have shown that N-myc has a number of functions during development, including a role in branching morphogenesis in the lung, which manifests itself at birth in mice homozygous for the leaky allele, and roles in the development of the mesonephric tubules, the neuroepithelium, the sensory ganglia, the gut and the heart, which become evident at midgestation in embryos homozygous for the null allele. In an attempt to define roles for N-myc at other stages of development, we have combined the two types of N-myc mutant allele in a compound heterozygote that as a result contains approximately 15% of normal levels of N-Myc protein. Compound heterozygotes died during gestation at a time intermediate to the times of death of embryos homozygous for either mutation individually, and their death appeared to result from cardiac failure stemming from hypoplasia of the compact subepicardial layer of the myocardium. Investigation of the expression pattern of N-myc and various markers of differentiation in wild-type and compound heterozygote mutant hearts has suggested that N-myc may function in maintaining the proliferation and/or preventing the differentiation of compact layer myocytes. This study illustrates the importance of generating different mutations at a given locus to elucidate fully the function of a particular gene during development.
KW - Heart development
KW - Mouse mutant
KW - N-myc
KW - Targeted mutagenesis
UR - http://www.scopus.com/inward/record.url?scp=0027436980&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0027436980&partnerID=8YFLogxK
M3 - Article
C2 - 8287798
AN - SCOPUS:0027436980
VL - 119
SP - 485
EP - 499
JO - Development (Cambridge)
JF - Development (Cambridge)
SN - 0950-1991
IS - 2
ER -