Aldh1a3 Conditional 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 conditional knockout mice carry a floxed allele so you delete function only where Cre is active. The germline allele stays intact until you cross to a tissue specific Cre. Labs reach for this design when a global knockout is lethal, when they need adult onset loss, or when regional redundancy hides a whole body phenotype.