All Phenotypes Slc3a1<tm1Jat> MGI Mouse

cystinuria ( J:254803 , J:254981 )

	• both males and females develop cystinuria (J:254981)
	(J:254803)

abnormal urinary bladder detrusor smooth muscle morphology ( J:254981 )

• males show smooth muscle hypertrophy and basement membrane thickening of varying degrees

nephrolithiasis ( J:254981 )

• males develop cysteine stones in the kidney but to a lesser degree than in the bladder

ureter obstruction ( J:254981 )

• males exhibit partial bladder outlet obstruction due to bladder stones

increased urinary bladder weight ( J:254981 )

• bladder weight of males is 4-fold higher than in controls and males exhibit an increase in bladder mass

cystolithiasis ( J:254803 , J:254981 )

• mice accumulate urinary bladder stones at an average rate of 1 mm³/day (J:254803)

• mice treated with tiopronin, a sulfhydryl drug, or L-cystine dimethylester show no difference in cystine stone growth rate (J:254803)

• treatment with the pro-antioxidant sulforaphane has a modest effect on cystine stone growth while treatment with alpha-lipoic acid strongly suppresses stone growth (J:254803)

• males treated with alpha-lipoic acid before stone formation show delayed stone formation, lower overall stone volume accumulation, and form fewer stones (J:254803)

• males treated with alpha-lipoic acid after forming stones show reduced growth rate of existing stones and withdrawal of alpha-lipoic acid results in reversion of stone growth rate (J:254803)

• all males develop cysteine stones in the bladder, ranging in number of and size of stones (J:254981)

• however, females do not exhibit bladder stones (J:254981)

abnormal urinary bladder physiology ( J:254981 )

• intravesical pressure at capacity is lower in females but is normal in males

• both males and females show poor compliance (rate of intravesical pressure rise over the first 20% bladder volume) compared to controls, with males being worse than females

impaired contractility of urinary bladder detrusor smooth muscle ( J:254981 )

• both maximal contractile response and the rate of tension generation (contractile responses to neurogenic stimulation) are reduced in males, with mice responding between 20-30% of the response of controls

• the contractile responses to ATP (purinergic receptor agonist), KCl (smooth muscle membrane depolarization), and carbachol (muscarinic agonist) are also decreased in males

• females show slightly decreased contractile responses

• however, the contractile response to phenylephrine (alpha-adrenergic agonist) is normal

abnormal bladder urine volume ( J:254981 )

• the volume at capacity of bladder is lower in males

• females exhibit increased volume compared to males

abnormal urination ( J:254981 )

• females exhibit decreased voiding pressure