Phenotypes associated with this allele

• Allele Symbol: Slc14a1^tm1Ask
• Allele Name: targeted mutation 1, Alan S Verkman
• Allele ID: MGI:2182112
• Summary: 4 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Slc14a1^tm1Ask/Slc14a1^tm1Ask	involves: C57BL/6J	MGI:3033385
hm2	Slc14a1^tm1Ask/Slc14a1^tm1Ask	involves: C57BL/6J * CD-1	MGI:3822914
cx3	Aqp1^tm1Ask/Aqp1^tm1Ask Slc14a1^tm1Ask/Slc14a1^tm1Ask	involves: C57BL/6J	MGI:3033387
cx4	Slc14a1^tm1Ask/Slc14a1^tm1Ask Slc14a2^tm1Bxy/Slc14a2^tm1Bxy	involves: C57BL/6J	MGI:5304901

Genotype
MGI:3033385

hm1

• Allelic Composition: Slc14a1^tm1Ask/Slc14a1^tm1Ask
• Genetic Background: involves: C57BL/6J

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

homeostasis/metabolism

homeostasis/metabolism phenotype ( J:179936 )

N • creatinine plasma levels and clearance are normal

abnormal blood homeostasis ( J:75466 )

• plasma urea significantly increased

• urine/plasma osmolality ratio about 1/3 lower relative to wild-type mice

increased blood urea nitrogen level ( J:179936 )

abnormal urine homeostasis ( J:75466 )

• urinary urea significantly decreased

• urine/plasma osmolality ratio about 1/3 lower relative to wild-type mice

decreased urine creatinine level ( J:179936 )

• on standard chow or when fed a high-protein diet

decreased urine osmolality ( J:75466 , J:179936 )

• osmolality of urine was reduced (J:75466)

• on standard chow or when fed a high-protein diet (J:179936)

decreased urine urea nitrogen level ( J:179936 )

renal/urinary system

abnormal urine homeostasis ( J:75466 )

• urinary urea significantly decreased

• urine/plasma osmolality ratio about 1/3 lower relative to wild-type mice

decreased urine creatinine level ( J:179936 )

• on standard chow or when fed a high-protein diet

decreased urine osmolality ( J:75466 , J:179936 )

• osmolality of urine was reduced (J:75466)

• on standard chow or when fed a high-protein diet (J:179936)

decreased urine urea nitrogen level ( J:179936 )

abnormal renal filtration rate ( J:179936 )

• urea clearance is reduced compared to in wild-type mice

• following acute urea loading, mice exhibit defective early and late phase concentration of urea in the urine compared with wild-type mice

polyuria ( J:75466 , J:179936 )

• moderately polyuric (J:75466)

• excrete approximately 50% more fluid than normal (J:75466)

behavior/neurological

increased fluid intake ( J:179936 )

Genotype
MGI:3822914

hm2

• Allelic Composition: Slc14a1^tm1Ask/Slc14a1^tm1Ask
• Genetic Background: involves: C57BL/6J * CD-1

reproductive system

abnormal testis development ( J:125840 )

♂ • testicular development occurs earlier in mutant males than in wild-type males

♂ • testis weight of mutant males is significantly greater than in wild-type males from day 17 onward

♂ • numerous elongating spermatids are detected as early as 24 days of age

abnormal Sertoli cell development ( J:125840 )

♂ • Sertoli cell development occurs earlier in mutant males, as shown by an earlier elevation of follicle-stimulating hormone receptor (FSHR) and androgen binding protein (ABP) mRNA expression levels relative to wild-type levels (10 vs 17 days after birth, respectively)

increased testis weight ( J:125840 )

♂ • at 84 days of age, mutant testes weigh significantly more than wild-type testes (103.7 6.9 mg vs 80.3 6.7 mg, respectively)

♂ • the ratio of testis weight to body weight is 0.31 0.02% in mutant males and 0.22 0.03% in wild-type males

♂ • however, no significant differences are noted in the percentage of water content using wet-to-dry weight ratios

abnormal testis physiology ( J:125840 )

♂ • at 84 days of age, testis urea concentrations in mutant males are significantly higher than those in wild-type males (57.5 2.6 mmol/kg tissue weight vs 46.9 1.5 mmol/kg tissue weight, respectively)

♂ • at 84 days of age, total testis urea content is 335.4 43.8 g in mutant males vs 196.3 18.2 g in wild-type males

♂ • after renal blood vessel ligation, [14C]urea distribution is selectively reduced in mutant testis relative to wild-type testis (7.5 2.3% vs 18 3.1%, respectively)

♂ • testis urea concentration in mutant males is already higher than that in wild-type mice at 10 days of age; this difference is pronounced with increasing age

abnormal spermatogenesis ( J:125840 )

♂ • unexpectedly, spermatogenesis occurs ~1 wk earlier in mutant males than in wild-type males, with elongated spermatids first appearing on day 24 vs day 32, respectively

♂ • however, male fertility, sperm morphology and sperm numbers appear largely normal

early sexual maturation ( J:125840 )

• sexual maturation occurs earlier in the male reproductive system, at least partly due to decreased urea flux across the blood-testis barrier and reduced urea exit from Sertoli cells at 10 days of age and beyond

• mutant males start breeding earlier than wild-type males by ~1 wk (first breeding ages are 48 3 days vs 56 2 days, respectively)

• elongating spermatids appear ~1 wk earlier in mutant testis than in wild-type testis

• Sertoli cell development occurs ~1 wk earlier in mutant males than in wild-type males

endocrine/exocrine glands

abnormal testis development ( J:125840 )

♂ • testicular development occurs earlier in mutant males than in wild-type males

♂ • testis weight of mutant males is significantly greater than in wild-type males from day 17 onward

♂ • numerous elongating spermatids are detected as early as 24 days of age

abnormal Sertoli cell development ( J:125840 )

♂ • Sertoli cell development occurs earlier in mutant males, as shown by an earlier elevation of follicle-stimulating hormone receptor (FSHR) and androgen binding protein (ABP) mRNA expression levels relative to wild-type levels (10 vs 17 days after birth, respectively)

increased testis weight ( J:125840 )

♂ • at 84 days of age, mutant testes weigh significantly more than wild-type testes (103.7 6.9 mg vs 80.3 6.7 mg, respectively)

♂ • the ratio of testis weight to body weight is 0.31 0.02% in mutant males and 0.22 0.03% in wild-type males

♂ • however, no significant differences are noted in the percentage of water content using wet-to-dry weight ratios

abnormal testis physiology ( J:125840 )

♂ • at 84 days of age, testis urea concentrations in mutant males are significantly higher than those in wild-type males (57.5 2.6 mmol/kg tissue weight vs 46.9 1.5 mmol/kg tissue weight, respectively)

♂ • at 84 days of age, total testis urea content is 335.4 43.8 g in mutant males vs 196.3 18.2 g in wild-type males

♂ • after renal blood vessel ligation, [14C]urea distribution is selectively reduced in mutant testis relative to wild-type testis (7.5 2.3% vs 18 3.1%, respectively)

♂ • testis urea concentration in mutant males is already higher than that in wild-type mice at 10 days of age; this difference is pronounced with increasing age

homeostasis/metabolism

abnormal blood homeostasis ( J:125840 )

• at 84 days of age, serum urea concentrations in mutant males are significantly higher than those in wild-type males (9.3 0.6 mM vs 7.6 0.1 mM, respectively)

• however, mutant serum urea concentrations do not vary with age

growth/size/body

decreased body weight ( J:125840 )

• at 84 days of age, mutant males display a lower body weight than wild-type males (33.1 3.0 g vs 36.4 2.1 g, respectively)

• however, no significant differences are observed in the ratio of kidney weight and liver weight to body weight

hematopoietic system

decreased spleen weight ( J:125840 )

• at 84 days of age, mutant males display a lower spleen weight than wild-type males

immune system

decreased spleen weight ( J:125840 )

• at 84 days of age, mutant males display a lower spleen weight than wild-type males

Genotype
MGI:3033387

cx3

• Allelic Composition: Aqp1^tm1Ask/Aqp1^tm1Ask; Slc14a1^tm1Ask/Slc14a1^tm1Ask
• Genetic Background: involves: C57BL/6J

mortality/aging

postnatal lethality, complete penetrance ( J:79279 )

• only about 50% survive to 10 days of age

• 100% mortality by 2 weeks of age

growth/size/body

postnatal growth retardation ( J:79279 )

• although normal in size at birth, mice are 30% smaller than normal by 11 days of age

hematopoietic system

high mean erythrocyte cell number ( J:79279 )

• red blood cell count somewhat elevated

increased hematocrit ( J:79279 )

abnormal mean corpuscular volume ( J:79279 )

• reduced water permeability of red blood cells

Genotype
MGI:5304901

cx4

• Allelic Composition: Slc14a1^tm1Ask/Slc14a1^tm1Ask; Slc14a2^tm1Bxy/Slc14a2^tm1Bxy
• Genetic Background: involves: C57BL/6J

homeostasis/metabolism

homeostasis/metabolism phenotype ( J:179936 )

N • creatinine plasma levels and clearance are normal

decreased urine creatinine level ( J:179936 )

• not as severe as in Slc14a1^tm1Ask homozygotes

increased blood urea nitrogen level ( J:179936 )

• not as severe as in Slc14a1^tm1Ask homozygotes

decreased urine osmolality ( J:179936 )

• not as severe as in Slc14a1^tm1Ask homozygotes

• however, mice fed a high-protein diet exhibit normal increase in urine osmolality

renal/urinary system

decreased urine creatinine level ( J:179936 )

• not as severe as in Slc14a1^tm1Ask homozygotes

decreased urine osmolality ( J:179936 )

• not as severe as in Slc14a1^tm1Ask homozygotes

• however, mice fed a high-protein diet exhibit normal increase in urine osmolality

abnormal renal filtration rate ( J:179936 )

• urea clearance is reduced compared to in wild-type mice but not as severely as in Slc14a1^tm1Ask homozygotes

• following acute urea loading, early phase concentration of urine urea is increased compared to in Slc14a1^tm1Ask homozygotes as in wild-type mice while late phase concentration of urea in the urine fails to occur as in wild-type mice

polyuria ( J:179936 )

• not as severe as in Slc14a1^tm1Ask homozygotes

behavior/neurological

increased fluid intake ( J:179936 )

• not as severe as in Slc14a1^tm1Ask homozygotes