Genetic and phenotypic studies of the dark‐like mutant mouse

Abstract

The dark-like (dal) mutant mouse has a pleiotropic phenotype that includes dark dorsal hairs and reproductive degeneration. Their pigmentation phenotype is similar to Attractin (Atrn) mutants, which also develop vacuoles throughout the brain. In further characterizing the testicular degeneration of dal mutant males, we found that they had reduced serum testosterone and developed vacuoles in their testes. Genetic crosses placed dal upstream of the melanocortin 1 receptor (Mc1r) and downstream of agouti, although dal suppressed the effect of agouti on pigmentation but not body weight. Atrn(mg-3J) and dal showed additive effects on pigmentation, testicular vacuolation, and spongiform neurodegeneration, but transgenic overexpression of Attractin-like-1 (Atrnl1), which compensates for loss of ATRN, did not rescue dal mutant phenotypes. Our results suggest dal and Atrn function in the same pathway and that identification of the dal gene will provide insight into molecular mechanisms of vacuolation in multiple cell types.

Attractin gene deficiency contributes to testis vacuolization and sperm dysfunction in male mice

“…To evaluate the physiological effects of Atrn in male reproduction system, we analyzed some reproductive phenotypes between Atrn null mutant mouse Atrn mg-3J and wild-type control males C3HeB/FeJ at different ages. Cota et al found that the testes appeared normal in the 3-month-old Atrn mg-3J , but significant vacuolation was noted in 56% of the 6-month old Atrn mg-3J [17] . In our study, we detected mild vacuolation in the testes of the 5-month-old mutant mice, the similar finding to that of Cota et al At the age of 3 months, the weights of testes and epididymes, the sperm activity and fertility rate revealed no significant differences between the mutant mice and the control ones.…”

“…Research also demonstrated that Atrn mg-3J showed some effects on testicular vacuolation, which was evidenced by adult-onset vacuolation in the seminiferous tubules and interstitial cells [17] . In the present study, we observed the pathological changes of the testes and epididymes of the male Atrn mg-3J mice and their wild-type counterparts, and investigated the testicular enzyme activity as well as the fertility potential of the sperms.…”

Subclavian artery occlusion causing acute myocardial infarction in a patient with a left internal mammary artery graft

“…The dispersion and aggregation of pigment in zebrafish pigment cells is regulated by signaling through the melanocortin 1 receptor (MC1R), where MC1R activity is required for dispersion (Richardson et al,2008). The pigmentation phenotype of dal mutant mice also involves the MC1R pathway, with their dark coat color representing increased MC1R signaling (Cota et al,2008). The mechanism by which loss of prolidase function causes hyperpigmentation remains unclear.…”

“…Mice homozygous for the autosomal recessive dark‐like ( dal ) mutation have a pleiotropic phenotype that includes darkly pigmented fur, small body size, reproductive degeneration, vacuolated cells at the cortical medullary junction of the adrenal gland, mild hydrocephalus, dense bone, and dark‐staining urine (Harris et al,2003; Cota et al,2008). Here, we show that dark‐like ( dal ) mice also develop congenital heart defects that include septal defects and significantly thickened ventricular walls due to cardiomyocyte hypertrophy.…”

RML prions act through Mahogunin and Attractin-independent pathways

“…Brain proteins were extracted in MES buffered saline containing 0.1% Triton-X100 and protease inhibitors from animals of the indicated genotypes and ages. Lysates were centrifuged through a discontinuous sucrose gradient as described in ref 40 . and fractions analyzed for the presence of the raft marker flotillin-1 by western blotting.…”