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Osmoregulatory defect in adult mice associated with deficient prenatal expression of six2.
- Source :
-
American journal of physiology. Regulatory, integrative and comparative physiology [Am J Physiol Regul Integr Comp Physiol] 2011 Sep; Vol. 301 (3), pp. R682-9. Date of Electronic Publication: 2011 Jun 08. - Publication Year :
- 2011
-
Abstract
- Suboptimal kidney development resulting from a genetic deficit in nephron number can have lifelong consequences that may lead to cardiorenal complications upon exposure to secondary insults in later life. To determine whether the inherited reduced renal reserve compromises the ability to handle osmotic stress in the adult animal, we challenged the heterozygous 3H1 Brachyrrhine (Br/+) mouse, which displays heritable renal hypoplasia associated with reduced embryonic six2 expression, to a solution of 2% NaCl for 5 days or to fluid restriction for 48 h. Blood chemistry, fluid intake, and physiological parameters, including renal measurements, were determined. Systemic hypertonicity by prolonged salt loading led to significant increases in plasma osmolality and plasma Na(+), along with polydipsia and polyuria, with a significant urine-concentrating defect that was resistant to DDAVP treatment in the adult Br/+ mouse compared with wild-type littermates. The Br/+ mouse also developed a significant increase in blood urea nitrogen at baseline that was further elevated when 2% NaCl was given. Fluid restriction for 48 h further enhanced plasma osmolality and plasma Na(+) responses, although the Br/+ mouse was evidently able to produce a small amount of concentrated urine at this time. Hypothalamic c-Fos expression was appropriately activated in the Br/+ mouse in response to both osmotic challenges, indicating an intact central neuroendocrine pathway that was not affected by the lack of congenital six2 expression. Collectively, our results demonstrate impaired osmoregulatory mechanisms consistent with chronic renal failure in the Br/+ mouse and indicate that six2 haploinsufficiency has a direct effect on postnatal fluid and electrolyte handling associated with fluid imbalance.
- Subjects :
- Analysis of Variance
Animals
Antidiuretic Agents administration & dosage
Blood Urea Nitrogen
Deamino Arginine Vasopressin administration & dosage
Drinking
Gene Expression Regulation, Developmental
Haploinsufficiency
Homeodomain Proteins genetics
Hypothalamus metabolism
Hypothalamus physiopathology
Kidney Concentrating Ability
Kidney Failure, Chronic genetics
Kidney Failure, Chronic physiopathology
Mice
Mice, Mutant Strains
Nephrons abnormalities
Nephrons drug effects
Nephrons physiopathology
Organogenesis
Osmolar Concentration
Polyuria genetics
Polyuria metabolism
Polyuria physiopathology
Proto-Oncogene Proteins c-fos metabolism
Saline Solution, Hypertonic administration & dosage
Saline Solution, Hypertonic metabolism
Sodium blood
Sodium Chloride, Dietary administration & dosage
Sodium Chloride, Dietary metabolism
Transcription Factors genetics
Kidney Failure, Chronic metabolism
Nephrons metabolism
Transcription Factors deficiency
Water-Electrolyte Balance drug effects
Water-Electrolyte Balance genetics
Subjects
Details
- Language :
- English
- ISSN :
- 1522-1490
- Volume :
- 301
- Issue :
- 3
- Database :
- MEDLINE
- Journal :
- American journal of physiology. Regulatory, integrative and comparative physiology
- Publication Type :
- Academic Journal
- Accession number :
- 21653879
- Full Text :
- https://doi.org/10.1152/ajpregu.00187.2011