Longjohn 3 Jackson; a remutation in the Npr3 gene. Son Yong Karst, Patricia F. Ward-Bailey, Richard Samples,et al.

Longjohn 3 Jackson (lgj-3J); a remutation in the Npr3 gene.

Son Yong Karst, Patricia F. Ward-Bailey, Richard Samples, Kenneth R. Johnson, Leah Rae Donahue and Muriel T Davisson.

Source of Support: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: Npr3^lgj-3J

Mutation (allele) name: longjohn 3 Jackson

Gene symbol: Npr3

Strain of origin: C57BL/6J

Current strain name: C57BL/6J-Npr3^lgj-3J/J

Stock #: 008188 This research was supported by grants NIH/NCRR Grant RR01183 to the Mouse Mutant Resource (M.T. Davisson, PI) and Cancer Center Core Grant CA34196.

Phenotype categories: skeleton/limbs

Abstract

This new spontaneous remutation has been identified and mapped to Chromosome 15 in the same region as Npr3^lgj. A direct test for allelism was set up with Npr3^lgj-2J and the results confirmed that this new mutation is a remutation of Npr3.

Origin and Description

The Npr3^lgj-3J mutation arose at the Jackson Laboratory in a colony of C57BL/6J mice in 2005 and was discovered by Sara C. Connolly. Like the previously described longjohn (lgj) mutation, homozygous Npr3^lgj-3J 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. Older homozygous mice are thinner than their littermates and display severe thoracic kyphosis and their digits are often banded, twisted and deformed. Mice carrying theNpr3^lgj-3Jmutation are viable and fertile.

Genetic Analysis

Using our standard MMR mapping procedures, a mouse homozygous for the Npr3^lgj-3J mutation was mated to a CAST/EiJ mouse. The F1 progeny from this cross were then intercrossed and produced 53 affected mice of which 21 were utilized for linkage analysis. The Npr3^lgj-3J mutation maps to Chromosome 15 proximal to D15Mit131 (NCBI 36 position 30.3 Mb) and is non-recombinant with D15Mit12 (NCBI 36 position 3.16 Mb), D15Mit11 (NCBI 36 position 9.6 Mb), and D15Mit177 (NCBI 36 position 12.3 Mb). Based on phenotype and map position similarities, a direct test for allelism test was set up by mating an Npr3^lgj-3J homozygous female with an Npr3^lgj-2^J heterozygous male. This mating produced 13 pups of which 4 had the mutant phenotype proving allelism.

Pathology

Our standard pathological screen of two Npr3^lgj-3J mutant mice at 6 weeks of age reports no lesions.

Hearing assessment by auditory brainstem response testing (ABR) of two Npr3^lgj-3J mutant mice and two controls, all at 3 months of age, showed that both controls had normal hearing, one mutant had a mild hearing loss and the other mutant had severe hearing loss. ABR testing performed on four Npr3^lgj-3J mutant mice at 3.5 months of age and two Npr3^lgj-3J mutant mice at 5 months of age showed all with elevated thresholds at all frequencies.

The eyes of two Npr3^lgj-3J mutant mice were electroretinogram (ERG) tested at age 5.5 months and were normal. The eyes of two homozygous Npr3^lgj-3J mice at 7 months of age were examined with an ophthalmoscope, and the results were normal except one eye had a cornea.

Acknowledgements

We thank Sara C. Connolly for discovery of the mutant, Rod Bronson and Coleen Marden for pathological screening, Chantal Longo-Guess for hearing assessment, Norm Hawes and Ron Hurd for the eye examinations.

The Jackson Laboratory