Phenotypes for Wfs1 MGI:5643859 MGI Mouse

decreased body weight ( J:157967 , J:221941 , J:221943 )

• males are smaller at 9 weeks of age, while females become lighter at 16 weeks of age (J:221943)

slow postnatal weight gain ( J:221943 )

• mice gain less weight than wild-type mice with age

weight loss ( J:221941 , J:221943 )

	• mutants lose more weight during a 48-hour trial in cage than wild-type mice (J:221941)
	• seen in males with age (J:221943)

homeostasis/metabolism phenotype ( J:157127 )

N	• males exhibit normal serum testosterone and FSH concentrations relative to wild-type males

abnormal blood homeostasis ( J:221943 )

• plasma c-peptide concentration is reduced in males

decreased circulating glucose level ( J:221943 )

• in females, the mean blood glucose concentration is lower than in wild-type mice at 32 weeks of age

• females exhibit impaired glucose tolerance with high insulin levels, a phenotype similar to type 2 diabetes

hyperglycemia ( J:221943 )

• from 24 weeks of age, the mean blood glucose concentration increases and continues to rise with age in males

decreased circulating insulin level ( J:221943 )

• males exhibit lower plasma insulin levels and mean insulin levels

• the proinsulin/insulin ratio in males is higher

• males develop diabetes at 24 weeks of age, with decreased plasma insulin levels, indicative of type I diabetes

increased circulating insulin-like growth factor I level ( J:157967 )

decreased circulating leptin level ( J:221941 )

• lower levels of plasma leptin in mutant males, but not in mutant females

• however, mice show normal mean plasma TSH and T4 levels

increased oxygen consumption ( J:221941 )

• mean oxygen consumption is higher in mutant females than mutant males, but not different from wild-type mice

• however, mice show normal carbon dioxide and heat production

impaired glucose tolerance ( J:157967 , J:221943 )

• both males and females have impaired glucose tolerance in the intraperitoneal glucose tolerance test at 30 weeks of age (J:221943)

decreased food intake ( J:221941 )

• mean food intake per body weight is lower in mutants than in wild-type mice

increased vertical activity ( J:221941 )

• mutant females rear more frequently than wild-type females

decreased copulatory plug deposition ( J:157127 )

• occurrence of vaginal plugs in mated wild-type female mice is significantly lower than in females mated with wild-type males

abnormal sperm flagellum morphology ( J:157127 )

• sperm exhibit significantly less proximal bent tails than wild-type sperm

abnormal sperm head morphology ( J:157127 )

• males exhibit significantly less abnormal sperm heads than wild-type males

abnormal spermatogonia morphology ( J:157127 )

• testis histology revealed a significantly lower number of spermatogonia than in wild-type males

decreased male germ cell number ( J:157127 )

• number of spermatogonia and sperm cells is significantly decreased in the seminiferous epithelium

increased sperm motility ( J:157127 )

• unexpectedly, mean percentage of motile sperm is higher than in wild-type males

• however, percentage of straight motility is normal

abnormal seminiferous tubule morphology ( J:157127 )

• seminiferous tubule lumina commonly show an irregular contour or the lumen may even be obliterated

• accumulation of eosinofilic luminal content is observed

• several segments of these tubules contain no spermatogenic cells at all

abnormal seminiferous tubule epithelium morphology ( J:157127 )

• seminiferous tubule epithelium contains a significantly reduced number of spermatogonia and Sertoli cells

• however, Leydig cell number and structure is normal

decreased Sertoli cell number ( J:157127 )

• testis histology revealed a significantly lower number of Sertoli cells than in wild-type males

reduced male fertility ( J:157127 )

• when 8- to 12-wk-old males are mated with wild-type females, pregnancy rate is significantly lower than that observed with wild-type males (15% versus 32%), with no significant change in litter size

• only 8 of 13 males sired pups, whereas all 13 controls males tested had at least one litter