Phenotypes associated with this allele

• Allele Symbol: Wfs1^tm1Koks
• Allele Name: targeted mutation 1, Sulev Koks
• Allele ID: MGI:3835761
• Summary: 5 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Wfs1^tm1Koks/Wfs1^tm1Koks	129S6/SvEvTac-Wfs1^tm1Koks	MGI:5643859
hm2	Wfs1^tm1Koks/Wfs1^tm1Koks	involves: 129S6/SvEvTac * C57BL/6	MGI:3835784
hm3	Wfs1^tm1Koks/Wfs1^tm1Koks	involves: 129S6/SvEvTac * C57BL/6J	MGI:7571495
ht4	Wfs1^tm1Koks/Wfs1^+	129S6/SvEvTac-Wfs1^tm1Koks	MGI:5643860
ht5	Wfs1^tm1Koks/Wfs1^+	involves: 129S6/SvEvTac * C57BL/6	MGI:3835785

Genotype
MGI:5643859

hm1

• Allelic Composition: Wfs1^tm1Koks/Wfs1^tm1Koks
• Genetic Background: 129S6/SvEvTac-Wfs1^tm1Koks

• ♀: phenotype observed in females
• ♂: phenotype observed in males
• N: normal phenotype

growth/size/body

decreased body size ( J:157967 )

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

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)

behavior/neurological

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

reproductive system

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

cellular

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

endocrine/exocrine glands

abnormal thyroid gland morphology ( J:221941 )

• epithelial cells and their nuclei are extremely flat in thyroid glands from mutant females

abnormal thyroid follicle morphology ( J:221941 )

• thyroid glands of females exhibit larger follicles

• thyroid glands of mutant males have smaller thyroid follicles, with a decrease in the mean number of epithelial cells per follicle (13.2 vs. 15.1), and an increase in the amount of intersititum

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

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
Wolfram syndrome 1		DOID:0110629	OMIM:222300	J:221941 , J:221943

Genotype
MGI:3835784

hm2

• Allelic Composition: Wfs1^tm1Koks/Wfs1^tm1Koks
• Genetic Background: involves: 129S6/SvEvTac * C57BL/6

mortality/aging

prenatal lethality, incomplete penetrance ( J:145548 )

• 5% fewer than expected mice are born

behavior/neurological

behavior/neurological phenotype ( J:145548 )

N • mice exhibit normal contextual fear conditioning, active avoidance, forced-swim behavior, and coordination on a rotarod

abnormal behavioral response to addictive substance ( J:145548 )

• amphetamine-stimulated activity is decreased compared to in similarly-treated wild-type mice

• apomorphinne induces a greater increase in locomotor activity compared to in similarly treated wild-type mice

abnormal cued conditioning behavior ( J:145548 )

• mice exhibit increased freezing in a cued conditioning test compared to wild-type mice

decreased exploration in new environment ( J:145548 )

• following short-term isolation, mice exhibit reduced exploration in a light-dark box exploration test compared to similarly treated wild-type mice

• mice exhibit decreased exploration in an elevated-plus maze compared to wild-type mice

• however, treatment with diazepam increases exploratory behavior

abnormal spatial learning ( J:145548 )

• mice exhibit impaired reverse spatial learning in a Morris water maze compared to wild-type mice

abnormal eating behavior ( J:145548 )

• mice exhibit a longer latency to start eating compared to wild-type mice

increased anxiety-related response ( J:150666 )

• increase in stretch-attend postures

• increase in open arm avoidance and affected risk assessment behaviors in a plus maze

increased thigmotaxis ( J:150666 )

• increase in open arm avoidance in a plus maze

impaired swimming ( J:145548 )

• slower swim speed

decreased vertical activity ( J:145548 )

• in a dark room

decreased locomotor activity ( J:145548 )

• under bright lights, mice exhibit decreased locomotor activity compared to wild-type mice

increased locomotor activity ( J:145548 )

• apomorphinne induces a greater increase in locomotor activity compared to in similarly treated wild-type mice

analgesia ( J:145548 )

• mice exhibit a greater stress-induced analgesic effect compared to in simialrly treated wild-type mice

abnormal vocalization ( J:145548 )

• 15% to 50% of mice produce spontaneous vocalizations above 10 kHz unlike wild-type mice

• vocalizations increase under stressful conditions

• however, vocalizations can be blocked by the administration of diazepam

homeostasis/metabolism

increased circulating corticosterone level ( J:145548 )

• stress-induced increases in plasma corticosterone levels are greater than in similarly treated wild-type mice

impaired glucose tolerance ( J:145548 , J:157967 )

• 30 and 60 minutes following intraperitoneal injection of glucose, mice exhibit increased serum glucose levels compared to wild-type mice (J:145548)

growth/size/body

decreased body size ( J:145548 , J:157967 )

• male mice are occasionally very small (J:145548)

decreased body weight ( J:145548 , J:150666 , J:157967 )

• at 2 and 3 months of age (J:145548)

slow postnatal weight gain ( J:145548 )

Genotype
MGI:7571495

hm3

• Allelic Composition: Wfs1^tm1Koks/Wfs1^tm1Koks
• Genetic Background: involves: 129S6/SvEvTac * C57BL/6J

hearing/vestibular/ear

abnormal inner hair cell stereociliary bundle morphology ( J:342760 )

• at age 10 months

cochlear outer hair cell degeneration ( J:342760 )

• at age 10 months

increased or absent threshold for auditory brainstem response ( J:342760 )

• higher ABR threshold at frequencies up to 10 kHz at age 4 months and all frequencies at age 10 months

impaired hearing ( J:342760 )

• higher auditory brainstem response (ABR) threshold at frequencies up to 10 kHz at age 4 months and all frequencies at age 10 months

nervous system

abnormal inner hair cell stereociliary bundle morphology ( J:342760 )

• at age 10 months

cochlear outer hair cell degeneration ( J:342760 )

• at age 10 months

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
nonsyndromic deafness		DOID:0050563		J:342760

Genotype
MGI:5643860

ht4

• Allelic Composition: Wfs1^tm1Koks/Wfs1⁺
• Genetic Background: 129S6/SvEvTac-Wfs1^tm1Koks

growth/size/body

decreased body weight ( J:157967 )

• intermediate

Genotype
MGI:3835785

ht5

• Allelic Composition: Wfs1^tm1Koks/Wfs1⁺
• Genetic Background: involves: 129S6/SvEvTac * C57BL/6

behavior/neurological

impaired behavioral response to addictive substance ( J:145548 )

• amphetamine-stimulated activity is decreased compared to in similarly-treated wild-type mice

homeostasis/metabolism

impaired glucose tolerance ( J:145548 )

• 30 minutes following intraperitoneal injection of glucose, mice exhibit increased serum glucose levels compared to in similarly treated wild-type mice

growth/size/body

decreased body weight ( J:157967 )

• intermediate