Description

Strain Information

Type Congenic; Mutant Strain; Additional information on Genetically Engineered Mutant Mice. Species Wild and outbred Swiss and M. m. domesticus Generation N6

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.

Related Strains

Strains carrying other alleles of Nek1

002854

C57BL/6J-Nek1kat-2J/J

View Strains carrying other alleles of Nek1     (1 strain)

Additional Web Information

Congenic Nomenclature

Phenotype

Phenotype Information

View Research Applications

Research Applications

This mouse can be used to support research in many areas including:

Nek1^kat related

Developmental Biology Research
Craniofacial and Palate Defects
Growth Defects
Internal/Organ Defects (brain)
Internal/Organ Defects (gonads)
Internal/Organ Defects (kidney)
Neurodevelopmental Defects
Postnatal Mortality

Hematological Research
Anemia, Iron Deficiency and Transport Defects

Internal/Organ Research
Kidney Defects

Neurobiology Research
Neurodevelopmental Defects

Reproductive Biology Research
Developmental Defects Affecting Gonads
Fertility Defects

Sensorineural Research
Olfactory Defects

Currently there is no phenotype information for this strain.

Genes & Alleles

Gene & Allele Information

Allele Symbol		Nek1kat
Allele Name		kidney, anemia and testis
Allele Type		Spontaneous
Common Name(s)		kat;
Strain of Origin		RBF/Dn
Gene Symbol and Name		Nek1, NIMA (never in mitosis gene a)-related expressed kinase 1
Chromosome		8
Gene Common Name(s)		D8Ertd790e; DKFZp686D06121; DKFZp686K12169; DNA segment, Chr 8, ERATO Doi 790, expressed; KIAA1901; MGC138800; NY-REN-55; kat; kidney, anemia and testis;
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).
Molecular Note		nucleotides 791-2105 deleted [MGI Ref ID J:59363]

Genotyping

Genotyping Information

This strain will not have a genotyping protocol or one is not currently available.

Helpful Links

Optimizing PCR Protocols

References

References

Additional References

Arama E; Yanai A; Kilfin G; Bernstein A; Motro B. 1998. Murine NIMA-related kinases are expressed in patterns suggesting distinct functions in gametogenesis and a role in the nervous system. Oncogene 16(14):1813-23. [PubMed: 9583679]  [MGI Ref ID J:47160]

Janaswami PM; Birkenmeier EH; Cook SA; Rowe LB; Bronson RT; Davisson MT. 1997. Identification and genetic mapping of a new polycystic kidney disease on mouse chromosome 8. Genomics 40(1):101-7. [PubMed: 9070925]  [MGI Ref ID J:37799]

Letwin K; Mizzen L; Motro B; Ben-David Y; Bernstein A; Pawson T. 1992. A mammalian dual specificity protein kinase, Nek1, is related to the NIMA cell cycle regulator and highly expressed in meiotic germ cells. EMBO J 11(10):3521-31. [PubMed: 1382974]  [MGI Ref ID J:2376]

Tanaka K; Parvinen M; Nigg EA. 1997. The in vivo expression pattern of mouse Nek2, a NIMA-related kinase, indicates a role in both mitosis and meiosis. Exp Cell Res 237(2):264-74. [PubMed: 9434622]  [MGI Ref ID J:45011]

Upadhya P; Birkenmeier EH; Birkenmeier CS; Barker JE. 2000. Mutations in a NIMA-related kinase gene, Nek1, cause pleiotropic effects including a progressive polycystic kidney disease in mice. Proc Natl Acad Sci U S A 97(1):217-21. [PubMed: 10618398]  [MGI Ref ID J:59363]

Nek1^kat related

Guay-Woodford LM. 2003. Murine models of polycystic kidney disease: molecular and therapeutic insights. Am J Physiol Renal Physiol 285(6):F1034-49. [PubMed: 14600027]  [MGI Ref ID J:87130]

Janaswami PM; Birkenmeier EH; Cook SA; Rowe LB; Bronson RT; Davisson MT. 1997. Identification and genetic mapping of a new polycystic kidney disease on mouse chromosome 8. Genomics 40(1):101-7. [PubMed: 9070925]  [MGI Ref ID J:37799]

Upadhya P; Birkenmeier EH; Birkenmeier CS; Barker JE. 2000. Mutations in a NIMA-related kinase gene, Nek1, cause pleiotropic effects including a progressive polycystic kidney disease in mice. Proc Natl Acad Sci U S A 97(1):217-21. [PubMed: 10618398]  [MGI Ref ID J:59363]

Vogler C; Homan S; Pung A; Thorpe C; Barker J; Birkenmeier EH; Upadhya P. 1999. Clinical and pathologic findings in two new allelic murine models of polycystic kidney disease. J Am Soc Nephrol 10(12):2534-9. [PubMed: 10589692]  [MGI Ref ID J:59839]

Health & husbandry

Health & Colony Maintenance Information

Currently there no information available for this strain. This may be due to the supply level of this strain.

Purchasing information

Pricing, Supply Level & Notes, Controls, General Terms & Conditions

Pricing

Supply Details

Standard Supply

Repository-Cryopreserved. Must Be Recovered. Please refer to pricing and supply notes for further information.

Supply Notes

Cryorecovery of Strains Needing Progeny Testing. The recovery process begins when a signed agreement form is returned to the Customer Service Department after order placement. Although results vary by strain, at least two untested males and two untested females (two pairs) will be recovered, typically within 15 weeks of our receipt of the signed agreement form. If the first recovery attempt is unsuccessful or only one pair is recovered, a second recovery will be done, extending the overall recovery time to approximately 25 weeks. However, all pups recovered will be sent. Progeny testing is required to identify the genotype of mice of this strain, as a genotyping assay is not available. This type of testing involves breeding the recovered animals and assessing the phenotype of the offspring in order to identify animals carrying the mutation of interest. We can perform the progeny testing for you as a service or we can ship all recovered animals (at least two untested pairs) to you for progeny testing at your facility. If you perform the progeny testing, there is NO guarantee that a carrier will be identified. If we perform progeny testing as a service, additional breeding time will be required. In this case, when a male and female (one pair) are identified that carry the mutation, they and their offspring will be shipped. Delivery time for strains requiring progeny testing often exceeds 25 weeks and may take 12 months or more due to the difficulties in breeding some strains. The progeny testing cost is in addition to the recovery cost and is based on the number of boxes used and the time taken to produce the mice identified as carrying the mutation. Please note that identified pairs may not reflect the mating scheme utilized by The Jackson Laboratory prior to cryopreservation of the strain. Mating schemes are sometimes modified for successful cryopreservation. Please contact Customer Service for more information on the cost of progeny testing for a strain: Tel: 1-800-422-6423 or 1-207-288-5845. Cryorecovery to establish a Dedicated Supply for greater quantities of mice One to two pairs will be recovered to establish a Dedicated Supply of mice. Price by quotation. For more information on Dedicated Supply, please contact JAX® Services, Tel: 1-800-422-6423 or 1-207-288-5845. Genomic DNA is available for this strain from the Mouse DNA Resource.

General Terms and Conditions

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The Jackson Laboratory has rigorous genetic quality control and mutant gene genotyping programs to ensure the genetic background of JAX^® Mice strains as well as the genotypes of strains with identified molecular mutations. JAX^® Mice strains are only made available to researchers after meeting our standards. However, the phenotype of each strain may not be fully characterized and/or captured in the strain data sheets. Therefore, we cannot guarantee a strain's phenotype will meet all expectations. To ensure that JAX^® Mice will meet the needs of individual research projects or when requesting a strain that is new to your research, we suggest ordering and performing tests on a small number of mice to determine suitability for your particular project.

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