STOCK Acan^cmd/NKruJ

Stock number: 010522
Product name: cartilage matrix deficiency (cmd)
Research areas: Developmental Biology Research, Endocrine Deficiency Research, Mouse/Human Gene Homologs, Neurobiology Research

Description

This spontaneous mutation of the aggrecan (Acan) gene displays homozygous perinatal lethality, cleft palate, shortened long bones, tail and snout. Heterozygous mice exhibit spinal curvature followed by a premature death at 19 months. This strain may be useful in studies of spinal degeneration and achondroplasia.

Detailed description

Mice that are homozygous for this spontaneous mutation die just after birth from an in ability to breathe. Newborns exhibit cleft palate, a protruding tongue, bulging abdomen, enlarged liver and a shortened trunk, limbs, snout and tail. Long bones measure half the length of wild-type mice and the spinal column is reduced by 25%. Cartilage in homozygous mice consists of densely packed chrondocytes, little matrix, pycnotic cells and unusual amounts of collagen fibers.

Mice that are heterozygous for the mutation appear normal at birth, but develop proportional dwarfism by 28 days. Aging mice exhibit spinal misalignment and degeneration followed by the sudden onset of a spastic gait and an accompanying decrease in movement. Mice die within one month following the appearance of the abnormal gait. Heterozygotes do not live beyond 19 months.

This mutant mouse strain may be useful in studies of achondroplasia, disc herniation and spinal degeneration.

Development

The cartilage matrix deficiency (cmd) mutation arose spontaneously on a mouse stock with mutations in T, t^low and tf in the laboratory of Dr. Bennett at Memorial Sloan-Kettering Cancer Center in 1978. At some point, the strain was transferred to the NIH and then, to Dr. Richard Krueger at the University of New Mexico, Albuquerque. The strain was initially maintained by sibling matings and, then, at the University of New Mexico by outcrosses to mice with both C57BL/6 and BALB backgrounds. Dr. Krueger donated this strain to The Jackson Laboratory in 2009. Upon arrival, mice were bred to C57BL/6J for at least 1 generation to establish the colony.

Allele

Symbol: Acan^cmd
Name: cartilage matrix deficiency
MGI accession ID: MGI:1856465
Generation method: Spontaneous
Marker symbol: Acan
Marker name: aggrecan
Marker synonyms: Agc; Agc1; AGCAN; b2b183Clo; CSPG1; CSPGCP; MSK16; SEDK; SSOAOD
Chromosome: 7
Strain of origin: STOCK T t^low Itpr3^tf
Molecular note: The molecular lesion is a 7 bp deletion in exon 5. Reduced mRNA levels are seen. The mutation disrupts the coding region corresponding to the B subdomain of the N-terminal globular G1 domain of the encoded protein, and introduces a frame-shift resulting in a truncated protein, if expressed.