The phenotype associated with the Nek1kat-2J allele is more severe than that of the Nek1kat allele. Mice homozygous for Nek1kat-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 Nek1kat 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 Nek1Kat-2J...
The phenotype associated with the Nek1kat-2J allele is more severe than that of the Nek1kat allele. Mice homozygous for Nek1kat-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 Nek1kat 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 Nek1Kat-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 Nek1kat 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 Nek1kat-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. Nek1kat homozygotes have similar renal cystic disease but the onset is slower relative to that in Nek1kat-2J homozygotes. (For morphologic details see Vogler et al., 1999.) Testicular hypoplasia with decreased spermatogenesis has been described for Nek1kat-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 Nek1Kat-2J homozygotes. (Janaswami et al., 1997; Vogler et al., 1999.)
The kat-2J allele arose spontaneously on the C57BL/6J background at The Jackson Laboratory in 1989 and has been maintained on this background. In 2000, C57BL/6J females were bred to heterozygous males to generate embryos for cryopreservation.
|Allele Name||kidney, anemia and testis 2 Jackson|
|Allele Synonym(s)||kat2J; kat2J|
|Gene Symbol and Name||Nek1, NIMA (never in mitosis gene a)-related expressed kinase 1|
|Gene Synonym(s)||D8Ertd790e; D8Ertd790e; DNA segment, Chr 8, ERATO Doi 790, expressed; NY-REN-55; SRPS2; SRPS2A; SRTD6; kat; kat; kidney, anemia and testis; kidney, anemia and testis|
|Strain of Origin||C57BL/6J|
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