Longjohn 4 Jackson (lgj-4J); A new remutation in the Npr3 gene

Belinda Harris, Patricia Ward-Bailey, Kenneth Johnson, and Roderick Bronson

Source of Support: The research was supported by NIH/NCRR grant RR01183 to the Mouse Mutant Resources (M.T. Davisson, PI) and Cancer Center Core Grant CA34196.

Mutation (allele) symbol: Npr3lgj-4J

Mutation (allele) name: longjohn 4 Jackson

Gene symbol: Npr3lgj-4J

Strain of origin: NOD/shiLtJ-wly/J

Current strain name:NOD/shiLtJ-Npr3lgj-4J/J

Stock #:008254 (Available as DNA only from the DNA Resource at The Jackson Laboratory.

Phenotype categories: skeletal/limbs

Abstract

We have identified a new remutation in the Npr3 gene which exhibits the same phenotype as the original long john mutation (Npr3 lgj) on Chromosome 15.

Origin and Description

This new spontaneous remutation was found in a research colony of NOD/shiLtJ-wly/J (wooly) mice in The Jackson Laboratory Mouse Mutant Resource in 2003. Like the previously described longjohn (lgj) mutation, homozygous Npr3lgj 4J/J mutant mice are easily distinguishable as early as 5-7 days of age by their elongated bodies, kinked tails and conical extension of the body. Npr3lgj-4J/J mutant mice have extra long bones, especially the digit and have kyphosis. Mice carrying the Npr3lgj 4J/J mutation are viable and fertile. 

Genetic Analysis

Using our standard mapping procedures a mouse homozygous for the Npr3lgj-4Jmutation was mated to a C57BL/6J mouse. The F1 progeny from this cross were then intercrossed and produced 54 affected mice of which 21 were utilized for linkage analysis. The Npr3lgj-4J mutation maps to Chromosome 15 proximal to D15Mit175 (NCBI 36 position 9.2 Mb) and distal to D15Mit229 (NCBI 36 position 41.9 Mb) and is non-recombinant with D15Mit265 (NCBI 36 position 12.9Mb) .

Based on phenotype and map position similarities, a direct test for allelism was set up by mating a female mouse homozygous for the Npr3lgj 4J mutation to a male mouse carrying the Npr3lgj mutation. This mating produced two affected mice out of 16 born with two born dead proving allelism.

Pathology

Our standard pathological screen showed that one nine week old homozygous Npr3lgj-4J male had a very odd shaped head where the cerebellum is, cervical area tissue appeared to have an open spine, and the mouse had otitis media. X-Rays done on one three week old homozygous male showed elongated long bones and spine. Hearing as assessed by auditory brainstem response testing (ABR) on one homozygote male and two control females showed all tested to be almost deaf by three months of age. This hearing loss due to age related hearing loss in the background NOD/shiLtJ-wly/J strain.

The eyes of two male homozygotes and two female and three male controls were examined with an opthalamascope and were determined to be normal.

Discussion

We have identified a remutation to longjohn with similarities to the original mutation on Chromosome 15. This remutation will be available from The Jackson Laboratory DNA Resource and no embryos will be cryopreserved.

 

Acknowledgements

The authors would like to thank Norm Hawes for eye examinations, Heping Yu for auditory brain stem analysis, and Coleen Marden for histological preparations.