International Mammalian Genome Society

The 15th International Mouse Genome Conference (2001)


POSTER 68 - Nell1: A CANDIDATE GENE FOR ENU-INDUCED RECESSIVE LETHAL MUTATIONS AT THE l7R6 LOCUS AND POTENTIAL MOUSE MODELS FOR HUMAN NEONATAL UNILATERAL CORONAL SYNOSTOSIS (UCS)

Cymbeline T Culiat
Life Sciences Division
Oak Ridge National Laboratory
P.O. Box 2009
Oak Ridge TN 37831-8077

Co-Authors: 1)Millsaps J, 1)Desai J, 2)Stanford B, 2)Hughes L, 2)Kerley M, 2)Carpenter D, 2&3)Rinchik EM
Institutions:   1)Graduate School of Genome Science & Technology, The University of Tennessee, 2)Life Sciences Division, Oak Ridge National Laboratory, 3)Dept. of Biochemistry, Cellular & Molecular Biology, The University of Tennessee

NELL1: A candidate gene for enu-induced recessive lethal mutations at the l7r6 locus and potential mouse models for human neonatal unilateral coronal synostosis (ucs)

A gene (l7R6) critical for late embryonic development and survival has been mapped proximal to the pink-eyed dilution (p) gene in mouse chromosome 7. Six independent ENU-induced alleles designated 88SJ, 335SJ, 2038SJ, 102DSJ, 11DSJ and 45DSJ all result in late-gestation/neonatal lethality.  l7R6 maps to a region homologous to human 11p15.1, that contains a very large gene for a protein kinase C binding protein, called NELL1. Human NELL1 has a 2433-bp coding region with at least 15 exons spread out in ~500 kb genomic distance. Because the human gene is so large, and because we recovered so many l7R6 alleles in a relatively small number of gametes, the mouse counterpart seemed a logical candidate for l7R6. To determine if l7R6 is Nell1, a near full-length (1920 bp) cDNA was generated and was used as a probe for Northern analysis of both wild-type and mutant animals.  Nell1 expression was detected from E10-E18, increasing as fetal development progresses and concentrating particularly in the head at E18. In wild-type adults, expression was predominantly in brain. Notably, a severely reduced level of Nell1 expression was detected in one allele (102DSJ).  Abnormal expression of human NELL1 is associated with unilateral coronal synostosis (UCS) in newborns, a condition where coronal sutures fuse early, resulting in abnormal head development and limb defects. Mouse hemizygotes recovered at either E18 or two hours after birth also exhibit both gross cranial and limb defects. This phenotype thus support the Northern analysis result indicating that Nell1 is l7R6 and that Nell1 mutations in mouse resemble major components of NELL1 defects in humans. Cloning and sequencing of RTPCR-derived cDNA clones from mutant and wild-type alleles are in progress. [Research sponsored by the Office of Biological and Environmental Research, U.S. Department of Energy under contract DE-AC05-00OR22725 with UT-Batelle, LLC.]


Abstracts * Officers * Bylaws * Application Form * Meeting Calendar * Contact Information * Home * Resources * News and Views * Membership

Base url http://imgs.org
Last modified: Saturday, November 3, 2012