- Model 16552 is a constitutive knock-in of murine Rab29 under control of the Pgk promoter generated by targeted transgenesis into the ROSA26 locus.
- Rab29 is a Rab GTPase that acts as a key regulator in vesicle trafficking and maintaining the endosome-trans-Golgi network structure. Rab29, together with LRRK2, plays a role in the retrograde trafficking pathway for recycling proteins.
- Rab29 is one of five genes located within the PARK 16 locus that has been linked to Parkinson's disease.
- Rab 29 is a direct substrate of LRRK2--a kinase protein in which autosomal dominant missense mutations are linked to Parkinson's disease through increased kinase activity. In addition, Rab29 is a regulator of LRRK2, controlling its localization and activation. Homozygous mice can be produced by breeding heterozygous females to heterozygous males, but production is very low. Taconic recommends breeding wild type C57BL/6NTac female by heterozygous male or heterozygous female by wild type C57BL/6NTac male.
- There is a substantial increase in Rab29 protein levels by western blot in brain, kidney, and distal colon, with a moderate increase in spleen, lungs, macrophages. See "Phenotypic Data" section below for more detail.
Genetic Background:
C57BL/6NTac Background Origin:
The Rab29 Mouse was generated by inserting a transgene containing a neo cassette, a Pgk promoter, the murine Rab29 open reading frame together with a Kozak sequence (GCCACC), the human growth hormone (hGH) polyadenylation signal and an additional polyadenylation signal into the ROSA26 via recombinase-mediated cassette exchange (RCME). The original purpose of the Neo cassette was to allow for positive selection for construct recombination in the ES cell stage. Once in place, the presence of the polyA sequence following the Neo construct prevents ‘read-through’ transcription from the endogenous ROSA26 locus. This allows for constitutive expression of Rab29 under control of the Pgk promoter. Targeting occurred in ES cells derived from C57BL/6NTac. Targeted ES cells were microinjected into BALB/c blastocysts to generate chimeras. Germline transmission occurred during an IVF expansion using chimeric males and C57BL/6NTac oocyte donors. The colony was maintained by mating wild type C57BL/6NTac females to heterozygous males and heterozygous females to wild type C57BL/6NTac males.
As of April 1, 2018, The Michael J. Fox Foundation for Parkinson's Research (MJFF) has instituted a new ordering policy for this model in an effort to prevent delays in order fulfillment, ensure models are shipped at the desired age, and maintain affordable pricing for all researchers accessing MJFF models. To achieve these goals, the new MJFF policy dictates that no one group can deplete the MJFF-sponsored colony. As such, orders will be limited to a total quantity of approximately 15-20 per researcher per month. Average lead time and age range may vary based on quantity and sex requested. Researchers requiring orders above this amount should establish a dedicated colony for their own use, either by breeding in-house or contracting with Taconic. For questions or concerns, please email
tools@michaeljfox.org.
Source:
Model Sponsor: The Michael J. Fox Foundation Color:
Black Species:
Mouse Initial Publication:
This model is not yet published.
