Male mice homozygous for the Fam3b knock-out have decreased hepatic insulin clearance and reduced hepatic glucose production in response to hyperinsulinemic conditions.
Brant R. Burkhardt, University of South Florida
Homozygotes are viable, fertile, normal in size and do not display any gross physical or behavioral abnormalities. No gene product (mRNA or protein) is detected by RT-PCR and Western blot analysis of pancreatic islets and small intestines from homozygotes. Male mice that are homozygous for the targeted mutation and 4 to 6 months of age exhibit higher blood glucose levels in glucose tolerance tests when compared to wildtype controls. Although, insulin sensitivity is normal in mutant mice, insulin levels are elevated after glucose stimulation (intraperitoneal glucose injection) due to decreased hepatic insulin clearance. Glucose intolerance is not observed in mutant female mice. Isolated pancreatic islets from male homozygotes have impaired glucose-stimulated insulin secretion and calcium signaling. Male homozygotes have reduced hepatic glucose production (HGP) and increased insulin-mediated HGP suppression conditions as determined by hyperinsulinemic-euglycemic clamp assays. Furthermore, male homozygotes display reduced expression of the critical gluconeogenic enzymes of glucose-6-phosphatase (G6P) and phosphoenolpyruvate carboxykinase (PEPCK) following a 24 hour fast as compared to wildtype controls as determined by RT-PCR.
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. This is the case for the strain above. 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 containing a Neo selection cassette was used to disrupt the transcriptional start site (TSS), secretion signal peptide (SP), and exons 1 and 2. The construct was electroporated into 129S6/SvEvTac derived TL1 embryonic stem (ES) cells. Correctly targeted ES cells were injected into C57BL/6 blastocysts. The resulting chimeric animals were crossed to C57BL/6 mice. Heterozygotes were intercrossed to produce homozygotes. The mice were then backcrossed to C57BL/6 for 7 generations (see SNP note below). 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, Brant Burkhardt|
|Allele Type||Targeted (Null/Knockout)|
|Gene Symbol and Name||Fam3b, family with sequence similarity 3, member B|
|Gene Synonym(s)||2-21; 9030624C24Rik; 9030624C24Rik; C21orf11; C21orf76; D16Jhu19e; D16Jhu19e; DNA segment, Chr 16, Johns Hopkins University 19; DNA segment, Chr 16, Johns Hopkins University 19, expressed; ORF9; ORF9; PANDER; PRED44; Pander; RGD1311662; RIKEN cDNA 9030624C24 gene; open reading frame 9|
|Strain of Origin||129S6/SvEvTac|
|Molecular Note||Exons 1 and 2 were replaced with a neomycin selection cassette in reverse orientation. This removed the transcriptional and translational start sites and the first 54 amino acids including the secretion signal peptide and helix A. mRNA was not detected in pancreatic islets, small intestine, liver, spleen, kidney, and brain by RT-PCR. Western blot analysis of pancratic islets demonstrated the absence of full length protein.|
|Mutations Made By|| |
Brant Burkhardt, University of South Florida
When maintaining a live colony, these mice can be bred as homozygotes.
When using the B6.129S6-Fam3btm1Bkht/J mouse strain in a publication, please cite the originating article(s) and include JAX stock #013788 in your Materials and Methods section.
|Heterozygous for Fam3b<tm1Bkht>|
The average number of mice provided from recovery of our cryopreserved strains is 10. The total number of animals provided,
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