Aldh1a3 Knockout mouse models

Aldh1a3, ortholog of human ALDH1A3, encodes RALDH3, the retinaldehyde dehydrogenase that supplies retinoic acid to ventral retina, olfactory and nasal epithelium, otic vesicle, and forebrain, complementing the dorsal RALDH1 domain to build the ocular retinoid gradient required for optic cup and choanal morphogenesis. Biallelic human loss-of-function variants cause autosomal recessive microphthalmia and anophthalmia, while amplified expression marks mesenchymal glioma and triple-negative breast tumor cells with elevated aldehyde detoxification capacity. Constitutive nulls die in the immediate neonatal period from obstructed nasal passages, so respiratory rescue or conditional floxed alleles are mandatory for postnatal retinal, metabolic, or tumor studies. Patient-derived missense knockins are preferable when the question concerns residual catalysis and dominant-negative tetramer poisoning rather than complete absence. Aldh1a1 and Aldh1a2 do not compensate in ventral retina or nasal epithelium, which is precisely why the eye phenotype is penetrant. Choose Six3-Cre or Rx-Cre for ocular questions and adipose or myeloid drivers for metabolic endpoints.

Aldh1a3 null animals are straightforward to genotype and phenotype when survival is acceptable. They remain a standard background for pharmacology, biomarker, and rescue studies.