Impaired contractility and detrusor hypertrophy in cavin-1-deficient mice.
Caveolae are membrane invaginations present in a variety of cell types. Formation of caveolae depends on caveolins and on the more recently discovered family of proteins known as the cavins. Genetic ablation of caveolin-1 was previously shown to give rise to a number of urogenital alterations, but the effects of cavin-1 deletion on urogenital function remain unknown. Here we characterised detrusor contractility and structure in cavin-1-deficient mice. Electron microscopy demonstrated essentially complete lack of caveolae in the knock-out detrusor, and immunoblotting disclosed reduced levels of cavin-3 and of all caveolin proteins. Bladder weight was increased in male knock-out mice, and length-tension relationships demonstrated a reduction in depolarisation-induced contraction. Contractility in response to muscarinic receptor activation was similarly reduced. Despite these functional changes, micturition patterns were similar in conscious and freely moving animals and diuresis was unchanged. Our breeding additionally disclosed that the number of knock-out mice generated in heterozygous crosses was lower than expected, suggesting embryonic/perinatal lethality. In conclusion, this is the first study to show that cavin-1 is critical for detrusor caveolae and for the overall contractility and structure of the urinary bladder.
Department of Experimental Medical Science, Lund University, Biomedical Centre, BMC D12, SE-221 84 Lund, Sweden.
Mardjaneh Sadegh
MS
Karbalaei
Catarina
C
Rippe
Sebastian
S
Albinsson
Mari
M
Ekman
Alva
A
Mansten
Bengt
B
Uvelius
Karl
K
Swärd
D000818:Animals; D021941:Caveolae / Q000473:pathology; D005260:Female; D006984:Hypertrophy / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D008297:Male; D008565:Membrane Proteins / Q000172:deficiency* / Q000235:genetics / Q000502:physiology; D051379:Mice; D018345:Mice, Knockout; D009119:Muscle Contraction / Q000235:genetics* / Q000502:physiology; D009130:Muscle, Smooth / Q000378:metabolism* / Q000473:pathology*; D016601:RNA-Binding Proteins; D001743:Urinary Bladder / Q000378:metabolism* / Q000473:pathology*; D014566:Urogenital System / Q000378:metabolism / Q000473:pathology
C112745:Cavin1 protein, mouse; D008565:Membrane Proteins; D016601:RNA-Binding Proteins