Chga knock-out mice exhibit elevated levels of epinephrine, norepinephrine, and dopamine excretion in the urine.
Geoffrey N. Hendy, McGill University
Chromogranin A is a member of the granin family of neuroendocrine secretory proteins and is found in secretory vesicles of neurons and endocrine cells, such as chromaffin cells of the adrenal medulla, paraganglia, enterochromaffin-like cells, beta cells of the pancreas, as well as cardiomyocytes, keratinocytes and granulocytes. It is co-stored and co-released with catecholamines. These mice carry a targeted mutation of the Chga (chromogranin A) gene in which exons 1 through 4 are replaced by a NEO cassette.
Mice that are homozygous for the targeted mutation are viable and fertile. No gene product (mRNA) is detected by Northern blot analysis of adrenal RNA from homozygotes.
Homozygotes exhibit elevated levels of epinephrine, norepinephrine, and dopamine excretion in the urine.
During backcrossing, the Y chromosome may not have been fixed to the C57BL/6 genetic background.
In an attempt to offer alleles on well-characterized or multiple genetic backgrounds, alleles are frequently moved to a genetic background different from that on which an allele was first characterized. It should be noted that the phenotype could vary from that originally described. We will modify the strain description if necessary as published results become available.
A targeting vector designed by Dr. Geoffrey N. Hendy (McGill University) containing a NEO cassette was used to disrupt exons 1 through 4. The construct was electroporated into 129 derived R1 embryonic stem (ES) cells. Correctly targeted ES cells were injected into BALB/c blastocysts. The resulting chimeric animals were tested for germline transmission. The donating investigator reports that the mice were then backcrossed to C57BL/6 for 10 generations (see SNP note below). During backcrossing, the Y chromosome may not have been fixed to the C57BL/6 genetic background. Upon arrival at The Jackson Laboratory, the mice were crossed to C57BL/6J (Stock No. 000664) at least once to establish the colony.
A 32 SNP (single nucleotide polymorphism) panel analysis, with 27 markers covering all 19 chromosomes and the X chromosome, as well as 5 markers that distinguish between the C57BL/6J and C57BL/6N substrains, was performed on the rederived living colony at The Jackson Laboratory Repository. While the 27 markers throughout the genome suggested a C57BL/6 genetic background, all 5 markers that determine C57BL/6J from C57BL/6N were found to be segregating. These data suggest the mice sent to The Jackson Laboratory Repository were on a C57BL/6N genetic background.
|Allele Name||targeted mutation 1, Geoffrey N Hendy|
|Allele Type||Targeted (Null/Knockout)|
|Gene Symbol and Name||Chga, chromogranin A|
|Strain of Origin||(129X1/SvJ x 129S1/Sv)F1-Kitl+|
|Molecular Note||A targeting construct was designed to replace exons 1-4 with a neomycin resistance gene. Adrenal expression of the protein was undetectable in mutants. There was no evidene of a read through transcript derived from the remaining exons.|
When maintaining a live colony, these mice can be bred as homozygotes.
When using the Chga- mouse strain in a publication, please cite the originating article(s) and include JAX stock #023853 in your Materials and Methods section.