BALB/cJ-Enpp1^asj-2J/GrsrJ

Stock number: 019107
Product name: ages with stiffened joints 2 Jackson
Research areas: Cardiovascular Research, Dermatology Research, Developmental Biology Research, Metabolism Research

Description

This spontaneous mutation, which causes extensive mineralization of the joints, arterial vasculature, the dermal sheath of vibrissae, and multiple internal organs, provides a model for generalized arterial calcification of infancy.

Detailed description

Homozygotes present with a slow, hobbling gait, hunched posture, and sickly appearance due to progressive mineralization of the joints and organs. The front paws have the earliest and most evident stiffening and by 12 weeks of age the whole body appears stiffened. While levels of plasma calcium and phosphorus are within normal limits, there is an 80% reduction in the inorganic pyrophosphate plasma levels compared with wildtype controls. The skin of the muzzle is highly mineralized and histology shows mineralization of the dermal sheath of vibrissae. There is extensive arterial mineralization in the descending thoracic aorta, carotid artery, heart, spleen, lung, eye, and kidney, with a slight increase in mineralization of the liver, which becomes severe when fed a high phosphorous/low magnesium diet. This high phosphorous/low magnesium diet not only increases mineralization of most tissues assessed in homozygotes it also causes mineralization of the kidney in heterozygotes. Enpp1^asj-2J homozygotes on this BALB/cJ background respond with a more severe phenotype to the high phosphorous/low magnesium diet than do the Enpp1^asj homozygotes on a C57BL/6J background. Progeny from heterozygous offspring show near-normal Mendelian inheritance indicative of complete penetrance with no embryonic loss.

Development

The ages with stiffened gait 2 Jackson mutation arose spontaneously in 2011 in the production colony of BALB/cJ at The Jackson Laboratory. This mutation has been maintained coisogenic on this background, primarily by cross-intercross sibling mating.

Allele

Symbol: Enpp1^asj-2J
Name: ages with stiffened joints 2 Jackson
MGI accession ID: MGI:5607149
Generation method: Spontaneous
Attributes: Null/Knockout
Marker symbol: Enpp1
Marker name: ectonucleotide pyrophosphatase/phosphodiesterase 1
Marker synonyms: 4833416E15Rik; ARHR2; CD203c; COLED; E-NPP1; Ly-41; M6S1; NPP1; NPPS; Pc1; PC-1; Pca; PCA1; Pca-1; PDNP1; twy
Chromosome: 10
Strain of origin: BALB/cJ
Molecular note: This alelle is a spontaneous deletion of 40,035 bp extending from intron 1, 2,376 bp upstream of exon 2, to the 3 prime untranslated region, 199 bp downstream of the stop codon in exon 25, with an insertion into this deletion site of a 74 bp fragment derived from the 3 prime UTR of this gene