Rab38 is what cell biologists call a small GTPase. Think of it as a tiny molecular delivery driver. Its job is to ferry pigment-making cargo (an enzyme called tyrosinase, plus a couple of partners called TYRP1 and DCT) from the cell’s main warehouse (the trans-Golgi network) into stage-II pigment compartments inside specialized cells called melanocytes.[1] That same delivery job happens in several different cell types around the body, not just in hair follicle melanocytes. Anywhere a cell uses one of a family of specialized compartments called lysosome-related organelles (LROs for short), Rab38 is part of the supply chain. Each of those tissues tells a slightly different story when the delivery never arrives.
The six known stations
1. Hair follicle melanocytes. Pigment never loads into the hair shaft.[1] Result: blonde coat color (rather than fully albino, because a related gene called Rab32 partially covers in skin and gives some residual pigment).[2]
2. Retinal pigment epithelium (the layer behind the retina). Pigment doesn’t fill the cells the way it does in agouti rats.[3] Result: mildly pale iris, some light sensitivity (photophobia). Blondes may prefer dim rooms in the day.
3. Lung type-II pneumocytes (the cells that make surfactant). The surfactant gets made, but the secretion compartments (lamellar bodies) end up engorged because the on-demand release machinery is off.[4] Most of the time this is silent. Under stress like an infection, a blonde may not re-coat her alveoli as quickly.[5] Predicted vulnerability; not directly proven in live-animal stress tests yet.
4. Platelet precursors in the bone marrow. Platelet dense granules don’t form.[6] This is the bleeding-and-clotting story: blondes may bleed a touch longer from a small nick, but are naturally protected from pathological clots that can cause stroke. Same defect, opposite outcomes by context. See the bleeding entry.
5. Mast cells. The granules that store histamine don’t fully mature.[7] Predicted result: blunted histamine release in a serious allergic reaction. Possibly protective against anaphylaxis. Cell-line evidence only; no in-vivo allergen-challenge data in Rab38-null rats yet.
6. Kidney proximal tubule cells. The cells that recycle filtered protein back into the bloodstream do a slightly less complete job. A small fraction of albumin slips into the urine.[8] Documented in the literature as mild lifelong proteinuria. This is NOT kidney failure. It’s a leaky recycler. The FHH rat strain’s kidney failure (which sometimes gets attributed to Rab38) is mostly OTHER genes in that strain’s background, not Rab38 by itself (a careful genetic analysis deconvolved this).[8]
What you would notice in daily life
Almost nothing. In a healthy, well-cared-for blonde roof rat, the Rab38-null state mostly shows up as: the coat color, mildly pale iris, slight light sensitivity. None of the internal effects (the platelets, the lung cells, the kidney tubules, the mast cells) produce visible symptoms in normal life. They’re subclinical findings the published literature can detect, not problems a pet owner can see.
Brian’s line has had blondes and agoutis living side by side for years. The blondes live as long, raise litters as reliably, and have the same easygoing disposition. The biology underneath is fascinating; the practical impact is small.
Want to walk through it interactively?
Our INNER SPACE: THE MISSING PIECES text adventure is exactly this tour, but from inside the rat’s body. An albino alien xenobiologist named Whitey rides shotgun in your submarine, and you visit each of the six stations one by one, watching the consequences live. About 70 turns. No installation needed; runs in your browser.
References
- [1] Oiso N et al. “The rat Ruby (R) locus is Rab38: identical mutations in Fawn-hooded and Tester-Moriyama rats derived from an ancestral Long Evans rat sub-strain.” Mammalian Genome 2004;15(4):307-314. PubMed.
- [2] Wasmeier C et al. “Rab38 and Rab32 control post-Golgi trafficking of melanogenic enzymes.” Journal of Cell Biology 2006;175(2):271-281. PubMed.
- [3] Loftus SK et al. “Mutation of melanosome protein RAB38 in chocolate mice.” Proceedings of the National Academy of Sciences 2002;99(7):4471-4476. PubMed.
- [4] Zhang L et al. “Rab38 targets to lamellar bodies and normalizes their sizes in lung alveolar type II epithelial cells.” American Journal of Physiology. Lung Cellular and Molecular Physiology 2011;301:L461-L477. PubMed.
- [5] Osanai K et al. “Exogenous gene transfer of Rab38 small GTPase ameliorates aberrant lung surfactant homeostasis in Ruby rats.” Respiratory Research 2017;18:70. PubMed.
- [6] “RAB38 defects cause platelet dense-granule storage-pool deficiency and bleeding tendency.” PubMed.
- [7] Azouz NP et al. “Decoding the regulation of mast cell exocytosis by networks of Rab GTPases.” Journal of Immunology 2012;189(5):2169-2180. PubMed.
- [8] Rangel-Filho A et al. “Rab38 modulates proteinuria in model of hypertension-associated renal disease.” Journal of the American Society of Nephrology 2013;24(2):283-292. PubMed.