C.129-Chga^tm1Gnh/J

Stock number: 023514
Product name: Chga-
Research areas: Endocrine Deficiency Research, Metabolism Research, Research Tools

Description

Chga knock-out mice exhibit elevated levels of epinephrine, norepinephrine, and dopamine excretion in the urine.

Detailed description

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.

Development

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

Symbol: Chga^tm1Gnh
Name: targeted mutation 1, Geoffrey N Hendy
MGI accession ID: MGI:3653689
Generation method: Targeted
Attributes: Null/Knockout
Marker symbol: Chga
Marker name: chromogranin A
Chromosome: 12
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.