AP4E1

AP-4 complex subunit epsilon-1 is a protein that in humans is encoded by the AP4E1 gene.

Function

The heterotetrameric adaptor protein (AP) complexes sort integral membrane proteins at various stages of the endocytic and secretory pathways. AP4 is composed of 2 large chains, beta-4 (AP4B1) and epsilon-4 (AP4E1; this gene), a medium chain, mu-4 (AP4M1), and a small chain, sigma-4 (AP4S1).

Clinical relevance

It is currently hypothesized that AP4-complex-mediated trafficking plays a crucial role in brain development and functioning.

Model organisms

Ap4e1 knockout mouse phenotype

Characteristic	Phenotype
Homozygote viability	Normal
Fertility	Normal
Body weight	Normal
Anxiety	Abnormal
Neurological assessment	Normal
Grip strength	Normal
Hot plate	Normal
Dysmorphology	Normal
Indirect calorimetry	Normal
Glucose tolerance test	Normal
Auditory brainstem response	Normal
DEXA	Normal
Radiography	Normal
Body temperature	Normal
Eye morphology	Normal
Clinical chemistry	Abnormal
Haematology	Abnormal
Peripheral blood lymphocytes	Normal
Micronucleus test	Normal
Heart weight	Normal
Brain histopathology	Abnormal
Eye Histopathology	Normal
Salmonella infection	Normal
Citrobacter infection	Normal
All tests and analysis from

Model organisms have been used in the study of AP4E1 function. A conditional knockout mouse line, called Ap4e1^{tm1a(KOMP)Wtsi} was generated as part of the International Knockout Mouse Consortium program — a high-throughput mutagenesis project to generate and distribute animal models of disease to interested scientists.

Male and female animals underwent a standardized phenotypic screen to determine the effects of deletion. Twenty four tests were carried out on homozygous mutant mice and four significant abnormalities were observed. Females displayed decreased vertical activity in an open field test, had an abnormal complete blood count, hypoferremia, and a decreased corpus callosum size and enlarged lateral ventricles.