From: Genetics and functions of the retinoic acid pathway, with special emphasis on the eye
Gene | Synonyms | MGI identification number | Mouse knockout phenotypes (homozygous null mutations) |
---|---|---|---|
Adh1 | Â | 87921 | Impaired metabolism of (and sensitivity to) ethanol and retinol [105,106,107] |
Adh7 | ADH4 | 87926 | Defective ethanol clearance and reduced metabolism of retinal to RA [105] |
Aldh1a1 | RALDH1 | 1353450 | Increased energy dissipation, insulin resistance, diet-induced obesity resistance [108], significantly reduced ability to convert retinol to retinoic acid in the liver [109] |
Aldh1a2 | RALDH2 | 107928 | Devoid of retinoic acid, die by E10.5 with impaired hindbrain development, failure to turn, lack of limb buds, heart abnormalities, reduced otocysts and a truncated frontonasal region [110,111,112,113,114] |
Aldh1a3 | RALDH3 | 1861722 | Neonatal death [115], persistent hyperplastic primary vitreous, thick neural retina and no vitreum [28], choanal atresia, ethmoturbinal hypoplasia, ventral lens rotation, short ventral retina, and no Harderian gland [66] |
Aldh1b1 | ALDHX | 1919785 | Increased fasting circulating glucose levels and decreased blood acetaldehyde clearance [116], defects in beta cell development and functionality, glucose intolerance, age-dependent hyperglycemia, and insulin resistance [117] |
Aldh8a1 | ALDH12 or RALDH4 | 2653900 | None Found |
Cyp1b1 | Â | 88590 | Protected from the acute bone marrow cytotoxic and preleukemic effects of DMBA [118], show a decreased incidence of DMBA-induced lymphomas [119], ocular drainage structure abnormalities (~ POAG) [120] |
Cyp26a1 | Â | 1096359 | Mid-late gestation lethal and exhibit spina bifida, caudal agenesis, and abnormalities of the kidneys, urogenital tract, hindgut, cervical vertebrae, and rostral hindbrain [121, 122], rescued by partial Aldh1a2 deletion [42] |
Cyp26b1 | Â | 2176159 | Lethal immediately after birth exhibiting respiratory distress [123], limb morphogenesis and proximal-distal patterning is disrupted in homozygous null fetuses [123, 124], abnormal spermatogenesis/oogenesis [125], arrested hair follicle development [126] |
Cyp26c1 | Â | 2679699 | Viable, exhibit normal CNS development with no apparent anatomical defects [127] |
Crabp1 | CRABP-I | 88490 | Phenotypically normal and fertile [128] |
Crabp2 | CRABP-II | Â | Postaxial polydactyly [129] |
Fabp5 | Â | 101790 | Impaired skin barrier function [130], resistance to diet-induced obesity (decreased adipose tissue and improved glucose tolerance) [131], and impaired cognitive function [132, 133] |
Rara | NR1B1 | 97856 | High neonatal mortality due to maternal cannibalization, failure to thrive, and excess mortality during the postnatal period, male survivors exhibit testicular degeneration [134,135,136] |
Rarb | NR1B2 | 97857 | |
Rarg | NR1B3 | 97858 | Stunted growth, homeotic transformations of the rostral axial skeleton and tracheal cartilage, Harderian gland agenesis, high postnatal mortality, and male sterility [135, 139], splenomegaly, and myeloproliferative disease, abnormal granulocytes [140] |
Rbp1 | CRBPI | 97876 | Increased adiposity, increased PPAR-gamma target gene expression [141], increased Rpb2 and Crabp2, elevated pancreatic RA [142], increased susceptibility to a diet deficient in vitamin A [143] |
Rbp2 | CRBPII | 97877 | Pups of homozygous dams fed a marginal retinol diet show increased neonatal lethality due to inadequate retinal transport to the fetus, abnormal retinol level and vitamin absorption [144] |
Rbp4 | Â | 97879 | Impaired retinal function in first month of life [145], insulin sensitivity [146] |
Rdh5 | Â | 1201412 | Impaired dark adaptation and at high bleaching levels, large increase in 11-cis-retinyl ester concentration [147] |
Rdh10 | Â | 1924238 | Mid-gestational lethality, reduced RA-signaling and abnormal limb, craniofacial, somite and cardiac morphology including microphthalmia [24] and dorsal pancreas agenesis [148] |
Rxra | NR2B1 | 98214 | Multiple organ defects and die of cardiac failure by E14.5, eye defects (retinal abnormalities, late corneal opacity), placental defects [149,150,151,152,153] . |
Rxrb | NR2B2 | 98215 | Partial embryonic and perinatal lethality, and surviving adult males are sterile due to defects in spermatogenesis [154] |
Rxrg | NR2B3 | 98216 | Neuron reduction in striatum, premature death and altered responses to the administration of dopamine antagonists [155] |
Stra6 | Â | 107742 | Seven-fold reduction in total ocular retinoids, photoreceptor anomalies, abnormal RPE, sclera, and choroid [20] |