International Mammalian Genome Society

The 16th International Mouse Genome Conference (2002)

Plenary Presentations * Oral Presentations *
Poster Presentations: Complex Genetics and Disease Modifiers * Developmental Genetics * Functional Genomics * Gene Discovery * Genetic Manipulations to Alter Gene Function * Mouse Models: Human Disease and Pharmacogenetics * Sequence Annotation and Comparative Analysis of Genomes *
Attendees * Sponsors * Table of Contents * Photographs * Awards

POSTER 39 - NELL1, A GENE CODING FOR A NOVEL PKC-BINDING PROTEIN IS A CANDIDATE FOR LATE-GESTATION RECESSIVE LETHAL MUTATIONS AT THE L7R6 LOCUS

J DESAI
The University of Tennessee

1) Hughes L, 1) Millsaps J, 2) Stanford B, 2) Kerley M, 2) Carpenter D, 2) Rinchik E, 2) Culiat C
1) Genome Science and Technology Graduate School, The University of Tennessee  2) Life sciences Division, Oak Ridge National Laboratory

A locus (l7R6) critical for late embryonic development and survival has been mapped proximal to the pink-eyed dilution (p) gene in mouse chromosome 7. Eight independent ENU-induced alleles designated 88SJ, 335SJ, 2038SJ, 102DSJ, 11DSJ, 45DSJ, 141DSJ and 244DSJ have been recovered for l7R6 and all result in late-gestation lethality. Complementation analysis of l7R6 mutations with p deletions maps the gene(s) to a region homologous to human 11p15.1 where a very large gene for a novel protein kinase C binding protein, called NELL1, is located. Because the human gene is so large, and we recovered so many l7R6 alleles in a relatively small number of gametes screened, the mouse Nell1 gene was evaluated as a candidate for l7R6.  Northern Blot analysis showed that Nell1 was normally expressed throughout fetal development and increases dramatically in the head at late gestation. In adult mice, expression was detected predominantly in brain. A severely reduced level of Nell1 expression was observed in the 102DSJ allele. Abnormal expression of human NELL1 is associated with unilateral coronal synostosis in newborns, a condition where coronal sutures fuse early, resulting in abnormal head development. l7R6 mutant embryos exhibit cranial, vertebral and limb defects. A mutation in the 335SJ allele was determined to be an AT/GC transition resulting in a cysteine to arginine substitution in the Nell1 protein.  The phenotype data, RNA analysis and mutation scanning indicate that l7R6 is Nell1. Studying [Research sponsored by the Office of Biological and Environmental Research, U.S. DOE under contract DE-AC05-00OR22725 with UT-Battelle, LLC.]