Mice homozygous for this targeted mutation exhibit an increase in adiposity without obesity, reduced energy expenditure and can develop salt sensitive hypertension. This mutant mouse strain may be useful in studies of energy homeostasis, regulation of satiety, salt-sensitive hypertension and metabolism.
Roger D. Cone, Vanderbilt University Medical Center
Mice that are homozygous for the targeted mutation are viable and fertile. Female homozygotes at approximately 50 to 60 days of age exhibit significantly heavier body weight when compared to heterozygotes. No gene product (mRNA) is detected by RT-PCR analysis of hypothalamus tissue. Male homozygotes exhibit an approximately 40% increase in body fat at 15-20 weeks of age when compared to wildtype. Heterozygotes display an intermediate increase in body fat percentage of approximately 36%. Although homozygotes have increased adiposity, there is no increased food intake or weight gain and resting basal or total oxygen consumption is lower in mutant mice when compared to wildtype. High fat diet causes an increased respiratory quotient within 24 hours of the diet change. Homozygotes on a low fat diet have a lower respiratory quotient than wildtype. Male homozygotes exhibit an approximately 50% decrease in wheel running behavior. Mutant mice become hypertensive with increased gamma-melanocyte-stimulating hormone plasma levels when placed on high sodium diet. Experimentally induced illness results in enhanced cachexia. This mutant mouse strain may be useful in studies of energy homeostasis, regulation of satiety, salt-sensitive hypertension and metabolism.
A targeting vector containing neomycin resistance and herpes simplex virus thymidine kinase genes was used to disrupt 0.7kb of encoding sequence including the initiation codon. The construct was electroporated into 129S4/SvJae derived J1 embryonic stem (ES) cells. Correctly targeted ES cells were injected into C57BL/6J blastocysts. The resulting chimeric animals were crossed to C57BL/6J mice, and then backcrossed to the same for more than 10 generations.
|Allele Name||targeted mutation 1, Roger D Cone|
|Allele Type||Targeted (Null/Knockout)|
|Gene Symbol and Name||Mc3r, melanocortin 3 receptor|
|Strain of Origin||129S4/SvJae|
|Molecular Note||0.7kb of sequence was replaced with a neomycin selection cassette at the initiation codon. Homozygous mutant mice were shown to lack transcript via RT-PCR analysis of total hypthalamic RNA.|
|Mutations Made By|| |
Jonathan Murphy, Oregon Health & Sciences University
When maintaining a live colony, these mice can be bred as homozygotes.
When using the B6.129S4-Mc3rtm1Cone/J mouse strain in a publication, please cite the originating article(s) and include JAX stock #007809 in your Materials and Methods section.