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 urine levels of epinephrine, norepinephrine, and dopamine secretion. During backcrossing, the Y chromosome may not have been fixed to the BALB/c genetic background.
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 male animals were crossed to BALB/c female mice, and then backcrossed to BALB/c for 11 generations. During backcrossing, the Y chromosome may not have been fixed to the BALB/c genetic background. Upon arrival at The Jackson Laboratory, the mice were crossed to BALB/cJ (Stock No. 000651) at least once to establish the colony.
|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 #023514 in your Materials and Methods section.