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Table 2 Mouse phenotypes for genes involved in the retinoic acid synthesis, degradation, and signaling

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   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   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   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   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   2679699 Viable, exhibit normal CNS development with no apparent anatomical defects [127]
Crabp1 CRABP-I 88490 Phenotypically normal and fertile [128]
Crabp2 CRABP-II   Postaxial polydactyly [129]
Fabp5   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 Reduced growth [137], locomotion abnormalities [138]
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   97879 Impaired retinal function in first month of life [145], insulin sensitivity [146]
Rdh5   1201412 Impaired dark adaptation and at high bleaching levels, large increase in 11-cis-retinyl ester concentration [147]
Rdh10   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   107742 Seven-fold reduction in total ocular retinoids, photoreceptor anomalies, abnormal RPE, sclera, and choroid [20]