| 2007 |
RDH10 catalyzes the first oxidative step of vitamin A metabolism — the oxidation of retinol to retinal — and is required for embryonic retinoic acid synthesis. A missense mutation in RDH10 (trex allele) abolishes this retinol dehydrogenase activity, resulting in insufficient RA signaling and craniofacial, limb, and organ defects. |
ENU forward genetic screen, protein modeling, enzymatic activity assays, and analysis of mutant embryos |
Genes & development |
High |
17473173
|
| 2004 |
RDH10 is expressed in retinal Müller cells (in addition to RPE) and its all-trans retinol dehydrogenase activity localizes to the microsomal fraction, using NADP as a preferred cofactor in those cells. It generates all-trans retinal, which serves as substrate for the photoisomerase RGR in Müller cells. |
Western blot, immunohistochemistry, RT-PCR, HPLC-based retinol dehydrogenase activity assay on microsomal fractions of rMC-1 cells |
Investigative ophthalmology & visual science |
Medium |
15505029
|
| 2008 |
Human RDH10 is a strictly NAD+-dependent enzyme (not NADP+-dependent as initially reported) with multisubstrate specificity, recognizing both all-trans-retinol and cis-retinols as substrates. It has an exceptionally low apparent Km for all-trans-retinol (~0.035 µM) but a relatively high Km for NAD+ (~100 µM). RDH10 functions exclusively in the oxidative direction in cells, increasing retinaldehyde and retinoic acid levels. siRNA-mediated knockdown of endogenous RDH10 in human cells significantly decreases retinoic acid production from retinol. |
Kinetic enzymatic assays with purified recombinant enzyme, cofactor specificity assays, siRNA knockdown with retinoid quantification |
The Journal of biological chemistry |
High |
18502750
|
| 2009 |
RDH10 oxidizes 11-cis-retinol to 11-cis-retinaldehyde in vitro (11-cis-RDH activity), stimulated by CRALBP. In a reconstituted visual cycle cell culture model (RDH10 + RPE65 + LRAT + CRALBP co-expression), 11-cis-retinaldehyde is generated from all-trans-retinol. RDH10 physically interacts with CRALBP and RPE65 by co-immunoprecipitation and co-localizes with them in bovine RPE cells. |
In vitro 11-cis-RDH activity assay in COS1 cells, reconstituted visual cycle in HEK-293A cells, co-immunoprecipitation, immunohistochemistry, HPLC retinoid profiling |
Investigative ophthalmology & visual science |
High |
19458327
|
| 2011 |
RDH10 is the primary retinol dehydrogenase responsible for the first oxidative step of embryonic vitamin A metabolism. The initial retinol-to-retinal conversion occurs predominantly in a membrane-bound cellular compartment, which prevents inhibition by cytosolic CRBP1 (RBP1). Cytosolic enzymes with RDH activity play a very limited role under normal dietary conditions. |
Rdh10trex mutant embryos, dietary retinaldehyde supplementation, RDH activity assays on membrane vs. cytosolic fractions |
Developmental biology |
High |
21782811
|
| 2011 |
RDH10 (via RA synthesis) is required for interdigital tissue loss but not for limb patterning per se. In Rdh10trex/trex mutants, RA activity is absent from limb mesoderm but present in neuroectoderm; restoration with 25 nM RA rescues RARE-lacZ activity in limb mesoderm. Meis2 and Shh expression and skeletal patterning are normal in Rdh10 mutant hindlimbs despite absent limb RA. |
RARE-lacZ RA-reporter transgene, exogenous RA rescue, skeletal staining, in situ hybridization in Rdh10trex/trex mutant embryos |
Developmental dynamics |
High |
21360789
|
| 2012 |
Rdh10 associates predominantly with mitochondria/mitochondrial-associated membrane (MAM) in the absence of lipid droplet biosynthesis, but relocates to lipid droplets during acyl ester biosynthesis. The 32 N-terminal residues (including a hydrophobic region followed by net positive charge) are required for lipid droplet targeting; both N-terminal and 48 C-terminal hydrophobic residues are required for mitochondria/MAM targeting and/or protein stability. Co-localization of Rdh10, CRBP1, and LRAT on lipid droplets suggests a metabolon for retinol homeostasis. |
Subcellular fractionation, domain deletion mutants, fluorescence colocalization, cell biology assays |
The Journal of biological chemistry |
Medium |
23155051
|
| 2013 |
In human monocyte-derived dendritic cells, RDH10, RALDH2, and CRABP2 form a linear PPARγ-regulated pathway required for ATRA production. All three proteins are co-regulated by PPARγ activation and all three are required for ATRA synthesis induced by PPARγ-activating fatty acids. |
siRNA knockdown of RDH10, RALDH2, and CRABP2 in human mo-DCs with ATRA measurement; PPARγ activation assays; colocalization in gut-associated lymphoid tissue DCs |
Journal of lipid research |
Medium |
23833249
|
| 2017 |
Rdh10 is specifically required in non-neural crest cells prior to E10.5 for proper choanae formation. Loss of Rdh10 leads to ectopic Fgf8 expression in the nasal fin, decreased cell proliferation, and increased cell death in the nasal cavity epithelium, retarding invagination and causing fully penetrant choanal atresia. |
Conditional/temporal Rdh10 mutant mouse analysis, cell lineage tracing, in situ hybridization for Fgf8, cell proliferation and apoptosis assays |
Human molecular genetics |
Medium |
28169399
|
| 2018 |
Rdh10 heterozygous hypomorphs produce ~25% less atRA in liver and adipose tissue, leading to escalated adipogenesis, increased adiposity under high-fat diet, liver steatosis, glucose intolerance, and insulin resistance. Embryonic fibroblasts with Rdh10 knockout show decreased atRA biosynthesis and escalated adipogenesis reversible by atRA or RAR pan-agonist treatment. |
Rdh10 heterozygote and knockout mouse models, atRA quantification by LC-MS, adipogenesis assays, metabolic phenotyping, pharmacological rescue with atRA |
Diabetes |
High |
29321172
|
| 2018 |
RDH10-mediated retinol metabolism and RARα-mediated RA signaling are required for submandibular salivary gland initiation. RDH10 and RALDH2 are expressed in the SMG mesenchyme at the initiation site, and ex vivo assays demonstrate that RDH10 and RA are both required for SOX9 expression and epithelial invagination. The RA requirement acts specifically through RARα with no contribution from other RAR isoforms. |
Ex vivo salivary gland initiation assay, stage-specific Rdh10 inactivation, RAR isoform-specific inhibitors/agonists, in situ hybridization |
Development (Cambridge, England) |
Medium |
29986869
|
| 2019 |
RDH10 function (via RA synthesis) is required for spontaneous fetal mouth movement that facilitates palate shelf elevation. Rdh10-deficient embryos display mispatterned pharyngeal nerves and skeletal elements that physically block fetal mouth movement in utero, causing cleft palate through a mechanical (movement-dependent) mechanism rather than a direct tissue defect in the palate shelf. |
Stage-specific Rdh10 inactivation, X-ray microtomography, in utero ultrasound video, ex vivo culture, tissue staining of pharyngeal nerves and skeletal elements |
Disease models & mechanisms |
Medium |
31300413
|
| 2007 |
Forced over-expression of RDH10 in HepG2 hepatocellular carcinoma cells increases endogenous RA concentration (measured by RARE-CAT reporter), causes antiproliferative effects without apoptosis, and is associated with upregulation of RARβ and p21Cip1 and downregulation of CyclinE/CDK2 mRNAs. |
Stable RDH10 over-expression in HepG2 cells, RARE-CAT reporter assay, RT-PCR for cell cycle gene expression, proliferation assays |
Cancer biology & therapy |
Low |
17218779
|
| 2025 |
Rdh10 knockout embryos fail to form a proper optic cup. Combined ChIP-seq (H3K27ac) and RNA-seq on eye tissue identified Alx1 as a direct RA target gene with an RA response element (RARE) near an RA-regulated H3K27ac mark. CRISPR/Cas9 knockout of Alx1 phenocopies Rdh10 KO in optic cup formation, placing Alx1 downstream of RDH10-mediated RA synthesis in eye development. |
Rdh10 knockout mouse, ChIP-seq for H3K27ac, RNA-seq on eye tissue, CRISPR/Cas9 Alx1 knockout, in situ hybridization |
bioRxivpreprint |
Medium |
bio_10.1101_2025.06.24.661406
|
| 2025 |
Rdh10 is highly expressed in the mesenchyme surrounding the entrance to the foregut and is essential between E7.5–E9.5 for vagal neural crest cell invasion into the gut. Rdh10 loss-of-function embryos exhibit intestinal aganglionosis; NCC form and migrate normally but fail to invade the foregut. RNA-seq revealed downregulation of the Ret-Gdnf-Gfrα1 signaling network and altered extracellular matrix (increased collagen deposition) in the NCC microenvironment. |
Rdh10 loss-of-function mouse, stage-specific inactivation (E7.5–E9.5), NCC lineage tracing, comparative RNA-seq, extracellular matrix analysis |
bioRxivpreprint |
Medium |
39896510
|