Phenotypes Associated with This Genotype

Genotype
MGI:5803956

• Allelic Composition: Aldh3a2^{tm1b(EUCOMM)Wtsi}/Aldh3a2^{tm1b(EUCOMM)Wtsi}
• Genetic Background: involves: C57BL * C57BL/6J * C57BL/6N * DBA

• ♀: phenotype observed in females
• ♂: phenotype observed in males
• N: normal phenotype

Vacuolization and broadened intercellular spaces in Aldh3a2^{tm1b(EUCOMM)Wtsi}/Aldh3a2^{tm1b(EUCOMM)Wtsi} epidermis

behavior/neurological

increased food intake ( J:234695 )

• food intake is slightly higher than in wild-type mice

• however, no differences in body weight are seen

cellular

increased keratinocyte proliferation ( J:234695 )

• keratinocytes exhibit enhanced proliferation

• however, mice do not exhibit hyperkeratosis

oxidative stress ( J:234695 )

• expression of oxidative stress-induced genes is increased in keratinocytes

homeostasis/metabolism

abnormal phospholipid level ( J:234695 )

• deuterium-sphingoinse is only slightly metabolized to phosphatidylcholine (PC) and phosphatidylethanolamine (PE) in keratinocytes, with PC and PE levels being 17.9 and 6.9% of those in wild-type cells and instead plasmanyl/plasmenylcholine and plasmanyl/plasmenylethanolamine levels are increased 10.4- and 22.2-fold, respectively

decreased aldehyde dehydrogenase activity ( J:234695 )

• fatty aldehyde dehydrogenase (FALDH) activity toward long-chain aldehydes in the liver, kidney, and retina is less than 10% of that in wild-type mice while in the brain, small intestine, testis, spleen, and dermis, it is 30-50% of that in wild-type mice

• FALDH activity toward C8:0 aldehyde is reduced 50-66% compared with wild-type activity

• primary keratinocytes show extremely low (5% of wild-type) FALDH activity towards the C16:0 aldehyde, however differentiated keratinocytes show 59.5% of wild-type activity

• however, FALDH activity toward long-chain aldehydes in the cornea, lung, and epidermis is similar to wild-type mice

abnormal lipid metabolism ( J:234695 )

• metabolism of long-chain bases to ester-linked glycerolipids is severely impaired

integument

abnormal epidermis stratum basale morphology ( J:234695 )

• intercellular spaces between keratinocytes are broadened in the stratum basale

abnormal epidermis stratum granulosum morphology ( J:234695 )

• small, intracellular vacuoles are seen in the stratum granulosum

abnormal epidermis stratum spinosum morphology ( J:234695 )

• small, intracellular vacuoles are seen in the stratum spinosum

delayed skin barrier formation ( J:234695 )

• mice exhibit delayed skin barrier recovery after acetone treatment to perturb the stratum corneum

abnormal keratinocyte physiology ( J:234695 )

• keratinocytes show altered metabolism of dihydrosphingosine to glycerolipids, however metabolism of dihydrosphingosine to sphingolipids is normal

• the amounts of fatty acid released from glycerolipids in keratinocytes is lower than in wild-type keratinocytes

increased keratinocyte proliferation ( J:234695 )

• keratinocytes exhibit enhanced proliferation

• however, mice do not exhibit hyperkeratosis