DW/J-Acd^acd/J

Stock number: 001595
Product name: adrenocortical dysplasia
Research areas: Cell Biology Research, Dermatology Research, Developmental Biology Research, Endocrine Deficiency Research, Internal/Organ Research, Reproductive Biology Research

Description

These mice carry a spontaneous mutation at the Acd locus characterized by darkened pigmentation, short, curly vibrissae, smaller overall size, and abnormal pelage.

Detailed description

acd/acd homozygotes can be distinguished from their wildtype (?/+) littermates by darkened pigmentation, short, curly vibrissae, smaller overall size, and abnormal pelage. Hair growth is retarded and lacks zigzag and guard hairs producing a sparse coat. There is heavy pigmentation in the nose, ears, body, feet and tail, and foci of melanin are also found in the skin and lymph nodes. Tail kinks or polydactyly of the hind feet are sometimes found and external genitalia are underdeveloped. It is rare for homozygotes to breed. Hydronephrosis is sometimes found in post-wean aged homozygotes resulting from focal hypertrophy of ureteral epithelium which causes ureteral blockage. The adrenals are abnormal in both males and females. Although the size of the medullary cells is normal, the cortical cells and nuclei are much larger than normal with nuclear inclusions and many mitochondria in the cytoplasm. These mitochondria have tubular cristae and cholesterol ester droplets, which are indicative of steroidogenic cells. The juxtamedullary X-zone of the adrenals is absent. The plasma levels of adrenocortical trophic hormone are elevated, and in young females, but not males, serum coticosterone levels are lower. FACS analysis reveals increased ploidy in many tissues. Adrenals show twice the number of tetraploid cells as is found in wildtype controls, and also an increase in the percent of cells with a higher than tetraploid DNA content. Spleen and thymus cells from newborns also show increased ploidy and a small percentage of cells with increased ploidy is found in cardiac muscle. Fewer mitotic figures and an uptake of tritiated thymidine into the enlarged nuclei indicate a failure in the normal mitotic pathway subsequent to S-phase. acd/acd homozygotes have significantly reduced viability. Approximately 40% die within 24 hours of birth and more than half of the homozygotes weaned die before 10 weeks of age. These mutants are much smaller at birth than wildtype siblings and this disparity in relative weights increases with age. Few homozygotes survive beyond six months of age. (Sweet et al., 1988; Shire and Beamer, 1990; Beamer et al., 1994.)

Development

The acd mutation arose spontaneously in the DW/J colony at The Jackson Laboratory in 1985. The Pit1^dw mutation was bred out of this substrain of DW/J and in 1994 ?/+ females at F26 were bred with acd/+ males to generate embryos for cryopreservation.

Allele

Symbol: Acd^acd
Name: adrenocortical dysplasia
MGI accession ID: MGI:1856658
Generation method: Spontaneous
Synonyms: acd
Marker symbol: Acd
Marker name: adrenocortical dysplasia
Marker synonyms: PIP1; PTOP; TINT1; TPP1
Chromosome: 8
Strain of origin: DW/J
Molecular note: This spontaneous mutation arose at The Jackson Laboratory in 1985. A point mutation (G to A) in the +5 position of the splice donor site in the third intron of the gene was revealed by DNA sequence analysis. RT-PCR analysis showed that aberrant transcripts were expressed from this allele, all of which are predicted to alter the reading frame of the protein.
General note: This mutation occurred in a subline of DW/J that lacks the Pou1f1^dw mutation. J:18027