The Arntl knock-out strain may be useful in studies of circadian rhythm, arthritis, ankylosis, and glucose homeostasis.
Dr. Joseph S. Takahashi, Univ Texas Southwestern Medical Ctr
These targeted mutation mice exhibit a loss of both behavioral and molecular circadian rhythms. When placed in constant darkness, the mice undergo an immediate loss of circadian rhythmicity. Locomotor activity is impaired in both light and constant dark cycles.
Reduced total activity is seen as the mice age. They display a progressive noninflammatory arthropathy. Little pathology is seen prior to 11 weeks of age, but virtually all homozygotes develop joint ankylosis due to flowing ossification of ligaments and tendons by 35 weeks of age. Bone density and articular cartilage are unaffected.
Inactivation of the gene suppresses diurnal variation in glucose and triglycerides. Gluconeogenesis is abolished in homozygotes, but the counterregulatory response of corticosterone and glucagon to insulin-induced hypoglycemia is retained. Homozygotes are viable but not fertile and have an increased mortality rate after 26 weeks of age. A truncated, non-functional protein is produced. This strain may be useful in studies of circadian rhythm, arthritis, ankylosis, and glucose homeostasis.
The helix-loop-helix domain within exon 4 and all of exon 5 were replaced with a neomycin resistance gene cassette. 129/Sv-derived GS1 embryonic stem (ES) cells were used to create the mutation. This line was backcrossed 14 times to C57BL/6 by the donating laboratory.
|Allele Name||targeted mutation 1, Christopher A Bradfield|
|Allele Type||Targeted (Null/Knockout)|
|Allele Synonym(s)||Bmal1-KO; Mop3-; bmal1-; mMop3-|
|Gene Symbol and Name||Arntl, aryl hydrocarbon receptor nuclear translocator-like|
|Gene Synonym(s)||Arnt3; BMAL1; BMAL1c; Bmal1; JAP3; MOP3; PASD3; TIC; bHLHe5|
|Strain of Origin||129/Sv|
|Molecular Note||A portion of exon 4 containing the helix-loop-helix coding domain and all of exon 5 were replaced by a neomycin selection cassette. A larger transcript, resulting from a cryptic splice site between exon 3 and the neomycin resistance gene, was detected byNorthern blot analysis. The polypeptide truncates 15 residues after this splice site, prior to the functional domains encoded by exon 4 in the wild-type locus.|
|Mutations Made By|| |
Dr. Christopher Bradfield, University of Wisconsin Medical School
When maintained as a live colony, hetetozygotes may be bred. It is recommended that females be disturbed as little as possible because they are prone to killing their litters. Homozygotes are viable, but both males and females are reportedly sterile.
The average number of mice provided from recovery of our cryopreserved strains is 10. The total number of animals provided,
their gender and genotype will vary. We will fulfill your order by providing at least two pair of mice, at least one animal of
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