B6.RBF(C3Fe)-Nek1^kat/J

Stock number: 001271
Product name: kidney, anemia and testis
Research areas: Developmental Biology Research, Hematological Research, Internal/Organ Research, Neurobiology Research, Reproductive Biology Research, Sensorineural Research

Description

These mice carry a spontaneous mutation at the Nek1 locus characterized by runting with blunted noses and small olfactory bulbs. They also have shortened life expectancies with high pre-weaning mortality.

Detailed description

The phenotype associated with the Nek1^kat-2J allele is more severe than that of the Nek1^kat allele. Mice homozygous for Nek1^kat-2J all die before one year of age, a third of those that survive weaning die suddenly before 100 days of age, and the reported median survival age is 211 days. Mice homozygous for Nek1^kat also have a shortened life expectancy with high pre-weaning mortality and a reported median survival of 286 days, but 22% were found to survive beyond 1 year. Both mutants are runted and have blunted noses with olfactory bulbs that are approximately half the normal size and lack most of the glomerular and external granular layers. In the brain there is dilation of the lateral and third ventricles, cerebral aqueduct and fourth ventricle along with large, fluid-filled cysts in the choroid plexus. Hydrocephalus occurs. Normochromic normocytic anemia is found and is more pronounced in Nek1^Kat-2J homozygotes, often detectable before weaning and progressing with age. By 7 to 8 months of age uremia with abnormally shaped erythrocytes can also be detected in the peripheral blood. The hematocrit levels of Nek1^kat homozygotes is lower than normal in the young, but a significant drop occurs after approximately 200 days of age then continues to decrease. Abdominal distention occurs as a result of extensive renal enlargement. At 5 days of age microscopic examination fails to detect any morphologic change in the kidneys of either mutant, but fluid-filled cysts and dilated proximal tubules and Bowman spaces are found as early as 1 month of age in Nek1^kat-2J homozygotes. The bilateral renal cystic disease progresses involving all levels of the nephron by 3 months of age, and after 6 months of age this progression becomes comparatively more rapid in the females. Disease progression includes growth of cysts and an increase in the number of cysts. Nek1^kat homozygotes have similar renal cystic disease but the onset is slower relative to that in Nek1^kat-2J homozygotes. (For morphologic details see Vogler et al., 1999.) Testicular hypoplasia with decreased spermatogenesis has been described for Nek1^kat-2J homozygotes, and male sterility is a characteristic of both Nek1 mutants. No histological abnormalities have been described in the ovaries and homozygous females can reproduce but litters are less frequent than from wildtype or heterozygous females. Focal portal bile duct proliferation and dilation have been found in the older Nek1^Kat-2J homozygotes. (Janaswami et al., 1997; Vogler et al., 1999.)

Development

The kat allele arose spontaneously on the RBF/Dn background, then at F66, at The Jackson Laboratory in 1986. It was backcrossed to C3HeB/FeJ three times then subsequently backcrossed to C57BL/6J and in heterozygous N5 and N6 males were bred to C57BL/6J females to generate embryos for cryopreservation.

Allele

Symbol: Nek1^kat
Name: kidney, anemia and testis
MGI accession ID: MGI:1858030
Generation method: Spontaneous
Marker symbol: Nek1
Marker name: NIMA (never in mitosis gene a)-related expressed kinase 1
Chromosome: 8
Strain of origin: RBF/Dn
Molecular note: Nucleotides 791-2105 are deleted.
General note: Homozygous mutant mice have a latent onset, slowly progressing form of polycystic kidney disease (PKD) with renal pathology similar to the human autosomal-dominant PKD OMIM 173900, OMIM 600666). In addition, mutant mice show pleiotropic effects that include facial dysmorphism, dwarfing, male sterility, anemia, and cystic choroid plexus (J:59363).