B6.Cg-Bloc1s6^pa/J

Stock number: 000024
Product name: pallid
Research areas: Dermatology Research, Hematological Research, Internal/Organ Research, Neurobiology Research, Sensorineural Research

Description

These mice carry a spontaneous mutation at the Bloc1s6 locus characterized by are pink eyes and a light, yellow-brown coat. Pallid mice have a deficiency in serum a1-antitrypsin and have been proposed as a model of genetic a1-antitrypsin deficiency. Lung lesions similar to those seen in human emphysema are found in these mice.

Detailed description

Mice homozygous for the pallid spontaneous mutation pa and nonagouti (a) are pink-eyed and have a light, yellow-brown coat. The coat is a little lighter than that of pink-eyed dilution homozygotes (p/p). Viability of homozygote mutant mice is slightly reduced. Some homoygotes have slightly abnormal behavior, with abnormal postural responses and head tilting due to the absence of otoliths in the sacculus and utriculus in many but not all mutant mice. The effect of pallid on behavior and otolith morphology appears to be a result of manganese deficiency. Homozygotes display defective mucopolysaccharide synthesis in the otolith matrix and a slower rate of transport of manganese, L-dopa, and L-tryptophane in the brain. Homozygotes have elevated basal and testosterone-induced levels of the kidney lysosomal enzymes b-glucuronidase, b-galactosidase, and a-mannosidase, accompanied by lowered enzyme excretion in the urine. Pallid mice have a deficiency in serum a1-antitrypsin and have been proposed as a model of genetic a1-antitrypsin deficiency. Lung lesions similar to those seen in human emphysema are found in these mice, and are attributed, like human hereditary emphysema, to a decreased capacity to inhibit serum elastase although liver a1-antitrypsin activity is normal. Pallid mice have prolonged bleeding time due to a platelet storage pool deficiency (SPD) characterized by a normal platelet number but a deficiency in the number of platelet dense granules and in the serotonin, ATP, and ADP content of the granules. Two other mouse coat color mutants, muted (Bloc1s5^mu) and mocha (Ap3d^mh), present a similar concatenation of pigment, otolith, and platelet SPD abnormalities, which also occur in human Hermansky-Pudlak syndrome.

Development

Pallid was found in a wild female mouse caught in the countryside in 1926 and brought into the laboratory of Elmer Roberts at Urbana Illinois. This female was bred with a pink-eyed, brown, nonagouti mate but no other breeding records are available from the early history of this mutation. It was maintained at the Jackson Laboratory by Dr. GD Snell in 1952. It was brother x sister bred until 1972 and then backcrossed onto C57BL/6J by ES Russell. It was cryopreserved in 1986 by mating homozygous B6.Cg-Bloc1s6^pa males at N45 to C57BL/6J females.

Allele

Symbol: Bloc1s6^pa
Name: pallid
MGI accession ID: MGI:1856982
Generation method: Spontaneous
Marker symbol: Bloc1s6
Marker name: biogenesis of lysosomal organelles complex-1, subunit 6, pallidin
Chromosome: 2
Strain of origin: wild
Molecular note: The C to T substitution at coding nucleotide 205 introduces a premature stop codon at arginine codon 69 (p.R69*) in pallid mice. Through Northern analysis, a single mRNA of about 2.5kb was found in reduced levels compared to wild-type.