Severe kyphosis (sky); a new skeletal mutation on Chromosome 14
Son Yong Karst, Patricia F. Ward-Bailey, Richard Samples, Kenneth R. Johnson, Leah Rae Donahue and Muriel T. Davisson
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: sky
Mutation (allele) name: severe kyphosis
Gene symbol: sky
Strain of origin: DBA/2J
Current strain name: DBA/2J-sky/J
Stock #: 006057 (view JAX® Mice Data Sheet for additional information including Price and Supply Information)
Phenotype categories: skeleton/limbs
Abstract
A new spontaneous recessive mutation arose at the Jackson Laboratory and has been named severe kyphosis (sky). This new skeletal mutation maps to Chromosome 14.
Origin and Description
Mice displaying severe kyphosis were found by Marijo Vollmer in a production colony of DBA/2J mice at the Jackson Laboratory. Mice homozygous for the sky mutation have open eyelids at birth and exhibit a progressive S-shaped kyphosis of the lumbar region of the spine that becomes very severe. Mice homozygous for the sky mutation also display a shortened trunk due to the severe kyphosis and their tails appear to be in a higher position than normal. Homozygous mice generally die between 3 and 6 months of age, however some have lived longer than 6 months. Homoyygotes do not breed.
Genetic Analysis
Using standard MMR mapping procedures, a mouse homozygous for the sky mutation was mated to a C57BL/6J mouse. The normal looking F1 progeny from this cross were then intercrossed and produced 105 affected mice that were utilized for linkage analysis. The sky mutation maps to Chromosome 14 between D14Mit10 (NCBI 36 position 13.3 Mb) and D14Mit50 (NCBI 36 position 21.81 Mb).
Pathology
Hearing as accessed by auditory brain stem response (ABR) testing of a mutant and control at one month of age, and two mutants at two months of age, reveals severe hearing loss in all mice tested. The hearing loss is due to the DBA/2J background strain which has early onset age related hearing loss (AHL), and is not due to the sky mutation.
The eyes of one homozygous mutant and a control at 4 weeks of age were examined with an opthalamascope. The homozygous mutant had a bad cornea, pupil, and iris. The cornea was vascular and the retina could not be seen.
A pathological screen of a sky/sky mutant showed in sagittal serial sections of the spine only degeneration of articular cartilage, which may be nonspecific. A homozygous mouse at 3 weeks of age showed degeneration of spinal particular cartilage. There are small granulomas in muscle and brown fat. Serial cross sections of brain had no lesions. A homozygous mouse at 11 days of age showed hypotonic spine. In lateral serial sections there are foci of periarticular carticular necrosis. There are also foci of fat necrosis.
Acknowledgements
We thank Marijo Vollmer for discovery of the mutant, Rod Bronson and Coleen Marden for pathological screening, Chantal Longo-Guess for hearing assessment, Norm Hawes for the eye examinations.
