B6;C-Rab29^{tm1b(EUCOMM)Wtsi}/McookJ

Stock number: 036852
Product name: Rab29^-
Strain synonyms: Rab29^- knock-out/lacZ
Research areas: Neurobiology Research, Research Tools

Description

Rab29^- knock-out/lacZ reporter mice lack exon 4 of the Rab29 (RAB29, member RAS oncogene family) coding sequence. Homozygous null mice develop diminished locomotor behavior. This strain may be useful for studies of Parkinson's disease.

Detailed description

Rab29 (RAB29, member RAS oncogene family) encodes a GTPase and is involved in membrane trafficking and intracellular signaling. RAB29 is one of 5 genes contained within the PARK16 locus associated with sporadic Parkinson's disease (PD) and is a substrate of LRRK2. Mutations in Rab29 are associated with increased risk for PD. Rab29^- knock-out/knock-in mice have exon 4 deleted and express a lacZ reporter. Mice homozygous for the mutation are viable and fertile. In the open field test, homozygotes exhibit reduced ambulatory count and less travel according to path length. The number of substantia nigra pars compacta dopamine neurons and tyrosine hydroxylase levels are not affected. Alone and in combination with an Lrrk2 KO, these mice be useful in studies of Parkinson's disease.

Development

Dr. Mark Cookson (NIA/NIH) obtained mice generated from clone EPD0418_1_B05 bearing the Rab29^{tm1a(EUCOMM)Hmgu} targeted allele. The construct was generated from a L1L2_Bact_P cassette inserted at position 131797953 of Chromosome 1 upstream of exon 4. The cassette is composed of an FRT site followed by lacZ sequence and a loxP site. This first loxP site is followed by neomycin under the control of the human beta-actin promoter, SV40 polyA, a second FRT site and a second loxP site. A third loxP site is inserted downstream of exon 4. Dr. Cookson bred these mice to B6.C-Tg(CMV-cre)1Cgn/J mice (Stock No. 006054) to remove the floxed neomycin and exon 4; mice retain the lacZ reporter. Mice were then outcrossed to C57BL/6J for at least 5 generations (see SNP note below). Upon arrival, mice were bred to C57BL/6J (Stock No. 000664) inbred mice for at least one generation to establish the colony.

In 2021, a 48 SNP (single nucleotide polymorphism) panel analysis, with 43 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 males sent to The Jackson Laboratory Repository. Three of the 43 markers throughout the genome were segregating with BALB/c, on Chromosomes 7, 12, and 18. Also, three of the 5 markers that determine C57BL/6J from C57BL/6N were found to be segregating, including the rd8 recessive mutation associated with retinal degeneration on Chromosome 1 within the Crb1 locus. These data suggest the mice sent to The Jackson Laboratory Repository were on a mixed genetic background.

Allele

Symbol: Rab29^{tm1b(EUCOMM)Wtsi}
Name: targeted mutation 1b, Wellcome Trust Sanger Institute
MGI accession ID: MGI:6825753
Generation method: Targeted
Attributes: Reporter; Null/Knockout
Marker symbol: Rab29
Marker name: RAB29, member RAS oncogene family
Marker synonyms: MGC:28972; MGC:36539; RAB7L; Rab7l1
Chromosome: 1
Strain of origin: C57BL/6N-A^tm1Brd
Molecular note: The construct is generated from a L1L2_Bact_P cassette inserted at position 131797953 of Chromosome 1 upstream of exon 4. The cassette is composed of an FRT site followed by lacZ sequence and a loxP site. This first loxP site is followed by neomycin under the control of the human beta-actin promoter, SV40 polyA, a second FRT site and a second loxP site. A third loxP site is inserted downstream of exon 4. Cre-mediated recombination removed the neo cassette and exon 4..