title: Targeted disruption of the mouse Npal3 gene leads to deficits in behavior, increased IgE levels, and impaired lung function.
abstract: The non-imprinted in Prader-Willi/Angelman syndrome (NIPA) proteins are highly conserved receptors or transporters. Translocation of NIPA genes were found in patients with Prader-Willi syndrome, and loss-of-function of the NIPA1 gene was identified in hereditary spastic paraplegia. The family of NIPA-like domain containing (NPAL) proteins is closely related to the NIPA proteins, but to date nothing is known about their function. Here, we could demonstrate that both human NPAL3 and mouse NPAL3 are ubiquitously expressed and encode highly conserved proteins. To further elucidate the function of the Npal3 gene, knockout (Npal3(-/-)) mice were generated. Intensive phenotypic analyses revealed that disruption of the Npal3 gene results in a pleiotropic phenotype. The function of the nervous system was impaired in both mutant males and females which could be demonstrated in behavioral tests. In addition, in NPAL3 mutants the number of NK cells was decreased and changes in IgM, IgG(2), and IgA were observed, indicating that the immune system is also affected. Interestingly, increased IgE levels as well as impaired lung functions were observed in mutant males but not in mutant females. It should be noted that the human Npal3 gene is located at 1p36.12-->p35.1, and atopic diseases were previously linked to this genomic region. Thus, the Npal3(-/-) mice could serve as a valuable model system for studying atopic diseases.
authors.affiliation: Institute of Human Genetics, University of Goettingen, Goettingen, Germany.
authors.forename: P
authors.initials: P
authors.lastname: Grzmil
authors.forename: J
authors.initials: J
authors.lastname: Konietzko
authors.forename: D
authors.initials: D
authors.lastname: Boehm
authors.forename: S M
authors.initials: SM
authors.lastname: Hölter
authors.forename: S M
authors.initials: SM
authors.lastname: Hoelter
authors.forename: A
authors.initials: A
authors.lastname: Aguilar-Pimentel
authors.forename: A
authors.initials: A
authors.lastname: Aguilar
authors.forename: A
authors.initials: A
authors.lastname: Javaheri
authors.forename: S
authors.initials: S
authors.lastname: Kalaydjiev
authors.forename: T
authors.initials: T
authors.lastname: Adler
authors.forename: I
authors.initials: I
authors.lastname: Bolle
authors.forename: I
authors.initials: I
authors.lastname: Adham
authors.forename: C
authors.initials: C
authors.lastname: Dixkens
authors.forename: S
authors.initials: S
authors.lastname: Wolf
authors.forename: H
authors.initials: H
authors.lastname: Fuchs
authors.forename: V
authors.initials: V
authors.lastname: Gailus-Durner
authors.forename: V
authors.initials: V
authors.lastname: Gailus-Durne
authors.forename: W
authors.initials: W
authors.lastname: Wurst
authors.forename: M
authors.initials: M
authors.lastname: Ollert
authors.forename: D H
authors.initials: DH
authors.lastname: Busch
authors.forename: D
authors.initials: D
authors.lastname: Busch
authors.forename: H
authors.initials: H
authors.lastname: Schulz
authors.forename: M Hrabe
authors.initials: MH
authors.lastname: de Angelis
authors.forename: P
authors.initials: P
authors.lastname: Burfeind
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001522:Behavior, Animal; D027682:Cation Transport Proteins; D002462:Cell Membrane / Q000378:metabolism; D017124:Conserved Sequence; D019143:Evolution, Molecular; D005260:Female; D015870:Gene Expression; D006801:Humans; D007073:Immunoglobulin E / Q000097:blood* / Q000276:immunology; D008168:Lung / Q000502:physiology*; D008297:Male; D008565:Membrane Proteins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D008969:Molecular Sequence Data; D010641:Phenotype; D010802:Phylogeny; D016415:Sequence Alignment
chemical_list: D027682:Cation Transport Proteins; D008565:Membrane Proteins; C543813:NIPAL3 protein, human; C543812:Npal3 protein, mouse; D007073:Immunoglobulin E