A mutation in mouse Pak1ip1 causes orofacial clefting while human PAK1IP1 maps to 6p24 translocation breaking points associated with orofacial clefting

Adam P Ross; M Adela Mansilla; Youngshik Choe; Simon Helminski; Richard Sturm; Roy L Maute; Scott R May; Kamil K Hozyasz; Piotr Wójcicki; Adrianna Mostowska; Beth Davidson; Iannis E Adamopoulos; Samuel J Pleasure; Jeffrey C Murray; Konstantinos S Zarbalis

doi:10.1371/journal.pone.0069333

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A mutation in mouse Pak1ip1 causes orofacial clefting while human PAK1IP1 maps to 6p24 translocation breaking points associated with orofacial clefting

Journal article

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A mutation in mouse Pak1ip1 causes orofacial clefting while human PAK1IP1 maps to 6p24 translocation breaking points associated with orofacial clefting

Adam P Ross, M Adela Mansilla, Youngshik Choe, Simon Helminski, Richard Sturm, Roy L Maute, Scott R May, Kamil K Hozyasz, Piotr Wójcicki, Adrianna Mostowska, …

PloS one, Vol.8(7), pp.e69333-e69333

2013

DOI: 10.1371/journal.pone.0069333

PMCID: PMC3723895

PMID: 23935987

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Abstract

Orofacial clefts are among the most common birth defects and result in an improper formation of the mouth or the roof of the mouth. Monosomy of the distal aspect of human chromosome 6p has been recognized as causative in congenital malformations affecting the brain and cranial skeleton including orofacial clefts. Among the genes located in this region is PAK1IP1, which encodes a nucleolar factor involved in ribosomal stress response. Here, we report the identification of a novel mouse line that carries a point mutation in the Pak1ip1 gene. Homozygous mutants show severe developmental defects of the brain and craniofacial skeleton, including a median orofacial cleft. We recovered this line of mice in a forward genetic screen and named the allele manta-ray (mray). Our findings prompted us to examine human cases of orofacial clefting for mutations in the PAK1IP1 gene or association with the locus. No deleterious variants in the PAK1IP1 gene coding region were recognized, however, we identified a borderline association effect for SNP rs494723 suggesting a possible role for the PAK1IP1 gene in human orofacial clefting.

Mutation

Amino Acid Sequence

Translocation, Genetic

Chromosome Breakpoints

Humans

Molecular Sequence Data

Male

Chromosome Mapping

Cleft Palate - genetics

Chromosomes, Human, Pair 6

Homozygote

Cleft Lip - genetics

Animals

Cleft Lip - pathology

Cleft Palate - pathology

Alleles

Female

Mice

Polymorphism, Single Nucleotide

Nuclear Proteins - genetics

Intracellular Signaling Peptides and Proteins - genetics

Protein Isoforms - genetics

Details

Title: Subtitle: A mutation in mouse Pak1ip1 causes orofacial clefting while human PAK1IP1 maps to 6p24 translocation breaking points associated with orofacial clefting
Creators: Adam P Ross - Department of Pathology and Laboratory Medicine, University of California Davis, Sacramento, California, United States of America
M Adela Mansilla
Youngshik Choe
Simon Helminski
Richard Sturm
Roy L Maute
Scott R May
Kamil K Hozyasz
Piotr Wójcicki
Adrianna Mostowska
Beth Davidson
Iannis E Adamopoulos
Samuel J Pleasure
Jeffrey C Murray
Konstantinos S Zarbalis
Resource Type: Journal article
Publication Details: PloS one, Vol.8(7), pp.e69333-e69333
DOI: 10.1371/journal.pone.0069333
PMID: 23935987
PMCID: PMC3723895
NLM abbreviation: PLoS One
ISSN: 1932-6203
eISSN: 1932-6203
Publisher: Public Library of Science; United States
Grant note: R37 DE008559 / NIDCR NIH HHS P30 ES005605 / NIEHS NIH HHS NIH DE08559 / NIDCR NIH HHS R01 AR062173 / NIAMS NIH HHS T32 GM007337 / NIGMS NIH HHS R01 DE008559 / NIDCR NIH HHS
Language: English
Date published: 2013
Academic Unit: Anatomy and Cell Biology; Stead Family Department of Pediatrics; Epidemiology; Pediatric Dentistry; Craniofacial Anomalies Research Center; Dental Research; Iowa Institute of Human Genetics
Record Identifier: 9984025452302771

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