The ENU induced mutation (Fbxl3Ovtm) on the BTBR inbred background results in an extended circadian period. These mice may be useful for studying circadian rhythm modulation.
Dr. Joseph S. Takahashi, Univ Texas Southwestern Medical Ctr
|Allele Type||Gene Symbol||Gene Name|
|Chemically induced (ENU)||Fbxl3||F-box and leucine-rich repeat protein 3|
|Allele Type||Gene Symbol||Gene Name|
|Spontaneous||Itpr3||inositol 1,4,5-triphosphate receptor 3|
|Allele Type||Gene Symbol||Gene Name|
Ovtm ENU-induced mutants contain an A to G transition at nucleotide in exon 5 of the F-box and leucine-rich repeat protein 3 (Fbxl3) gene that defines an amino acid change from isoleucine to threonine at residue 364. While homozygous males are viable, fertile, and normal in size, homozygous females are viable and normal in size, but are often infertile. FBXL3 is part of the SKP1-CUL1-F-box-protein (SCF) ubiquitin protein ligase complex which mediates phosphorylation-dependent ubiquitination. Homozygotes have a long circadian period of ~26 hours. These mice may be useful for studying circadian rhythm modulation.
Male BTBR T+ Itpr3tf/J mice (Stock No. 002282) were treated with N-ethyl-N-nitrosourea (ENU) and then bred to BTBR T+ Itpr3tf/J females. The resulting male pups were then bred to BTBR T+ Itpr3tf/J females to obtain second generation female mice, which were subsequently backcrossed to first generation males to obtain third generation mice. A mutagenesis screen was then performed to identify mutations that alter circadian periodicity. One of these mutants, with a 25.8 hour period length length segregates in autosomal semi-dominant-manner was termed Overtime (Ovtm). Further studies revealed the F-box and leucine-rich repeat protein 3 (Fbxl3) gene as a candidate gene for Ovtm. In Ovtm mice, Fbxl3 contains a A to G transition in exon 5 of the coding region that defines an amino acid change from isoleucine to threonine at residue 364. These mice have been backcrossed to BTBR T+ Itpr3tf/J prior to arrival at The Jackson Laboratory.
|Allele Type||Chemically induced (ENU)|
|Gene Symbol and Name||Fbxl3, F-box and leucine-rich repeat protein 3|
|Gene Synonym(s)||AU041772; AW212966; F-box and leucine-rich repeat protein 3a; FBL3; FBL3A; FBXL3A; Fbl3a; Fbxl3a; Fbxl3a; Ovtm; Ovtm; Play68; Play68; expressed sequence AU041772; expressed sequence AW212966; overtime; play 68|
|Strain of Origin||BTBR T+ Itpr3tf/J|
|Molecular Note||This phenotypic mutant was identified in an ENU mutagenesis screen. Subsequently, a single A to G transition was identified in exon 5. This results in the conversion of amino acid residue 364 from isoleucine to threonine.|
|Mutations Made By|| |
Dr. Joseph Takahashi, Univ Texas Southwestern Medical Ctr
|Gene Symbol and Name||Itpr3, inositol 1,4,5-triphosphate receptor 3|
|Gene Synonym(s)||IP3R; IP3R3; IP3R3X; Ip3r3; Ip3r3; Itpr-3; Itpr-3; inositol 1,4,5-triphosphate receptor, type III; tf; tf; tufted|
|Strain of Origin||BTBR|
|General Note||This allele was recovered from a Harwell testing stock carrying multiple recessive markers in an undefined background. (J:273)|
|Molecular Note||Complementation mapping was used to demonstrate that this spontaneous mutation was an allele of Itpr3. Sequencing revealed a 12 bp deletion in Exon23 (Chr17: 27238069, Build 38.1) which codes for amino acids 983-986. This mutation arose early in the history of the BTBR strain (in or soon after 1956) and is not found in 18 other strains (129P2/OlaHsd, 129S1/SvImJ, 129S5/SvEvBrd, A/J, AKR/J, BALB/cJ, C3H/HeJ, C57BL/6NJ, CAST/EiJ, CBA/J, DBA/2J, FVB/NJ, LP/J, NOD/ShiLtJ, NZO/HlLtJ, PWK/PhJ, SPRET/EiJ and WSB/EiJ)|
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