NCr nude

NCr nude

SPONTANEOUS MUTANT T-CELL DEFICIENT MICE

NCr Background

Nomenclature: CrTac:NCr-Foxn1nu

  • Outbred background originated from an accidental cross between the BALB/c inbred nude and NIH(S) outbred nude mice
  • The standard athymic model for National Cancer Institute (NCI) studies as well as many pharmaceutical and institutional oncology screening programs
  • Paralysis does seem to be a phenotype of NCR nude mice, however in measuring this phenotype in our colonies it is present in less than .04%
  • The autosomal recessive nude gene in homozygous (sp/sp) mice causes the lack of fur and an abnormal thymus. The deficiency in T cell function allows athymic mice to accept and grow xenografts as well as allografts of normal and malignant tissues.
  • Heterozygous (sp/wt) mice carry only one copy of the nude mutation and have hair. Heterozygous nudes were originally thought to have normal immune systems, but in fact have immune alterations such as reduced bone marrow stem cells and lower thymus weights. Heterozygous nudes may thus not be appropriate for use as sentinels. They may be used in PK/dosing studies.

 

Origin: Taconic received the NCr nude Spontaneous mutant model from NCI in 1993 after several years of random breeding. The mice were derived by hysterectomy to achieve Germfree status prior to introduction into Restricted Flora™ IBU™ colonies. These mice have both BALB/c inbred and NIH(S) outbred stock in their genetic background.

Coat Color Loci: Tyrc

Color: Albino

Species: Mouse

Animal Diet: NIH #31M Rodent Diet

Average litter size: 8
NCRNU Physiological Data Summary (March 2004; N=10/group):

 

Parameter Units NCR Nude Males NCR Nude Females
Serum Chemistry Avg ± S.D.
Calcium mg/dL 9.8 ± 0.4 10.6 ± 0.6
Phosphorous mg/dL 9.9 ± 1.0 9.6 ± 0.9
Glucose mg/dL 119 ± 17 91 ± 14
Creatinine mg/dL 0.2 ± 0.1 0.2 ± 0.0
BUN mg/dL 20 ± 3 25 ± 6
Total Bilirubin mg/dL 0.1 ± 0.0 0.1 ± 0.0
ALK U/L 259 ± 41 247 ± 41
ALT U/L U/L 53 ± 14 69 ± 43
Total Protein g/dL 5.9 ± 0.7 5.6 ± 0.2
Blood Counts
Erythron
Red Blood Cells X10^6/uL 10.01 ± 0.45 9.954 ± 0.387
Nucleated RBC X10^6/uL 0 ± 0 0 ± 0
Hemoglobin g/dL 16.3 ± 0.6 16.0 ± 0.4
Hematocrit % 51.1 ± 1.9 50.8 ± 1.4
MCV fL 51 ± 1 51 ± 1
MCH pG 16.3 ± 0.4 16.1 ± 0.3
MCHC % 31.8 ± 0.6 31.4 ± 0.4
Platelets
Platelets X10^3/uL 819 ± 327 897 ± 81
Leukogram
White Blood Cells x10^3/uL 5.0 ± 1.6 5.431 ± 1.901
Neutrophil x10^3/uL 2.287 ± 0.851 2.037 ± 1.323
Bands x10^3/uL 0 ± 0 0 ± 0
Lymphocyte x10^3/uL 2.603 ± 1.041 3.169 ± 0.989
Monocytes x10^3/uL 0.087 ± 0.098 0.139 ± 0.181
Eosinophil x10^3/uL 0.023 ± 0.040 0.082 ± 0.158
Basophils x10^3/uL 0 ± 0 0.0034 ± 0.0107
Others x10^3/uL 0 ± 0 0 ± 0
Organ Weights
Stomach g 0.200 ± 0.023 0.186 ± 0.019
Ileum g 0.737 ± 0.113 0.628 ± 0.087
Colon g 0.200 ± 0.044 0.186 ± 0.030
Lungs g 0.228 ± 0.014 0.196 ± 0.023
Heart g 0.186 ± 0.037 0.161 ± 0.028
Liver g 1.200 ± 0.067 1.014 ± 0.111
Spleen/Pancreas g 0.222 ± 0.025 0.202 ± 0.056
Kidney (L) g 0.207 ± 0.024 0.140 ± 0.017
Kidney (R) g 0.205 ± 0.023 0.146 ± 0.024
Testes (L) g 0.101 ± 0.011 –
Testes (R) g 0.104 ± 0.010 –
Ovary (L) g – 0.017 ± 0.005
Ovary (R) g – 0.013 ± 0.006
Urinalysis
Glucose mg/dL N/a N/a
Blood – N/a N/a
Ph – 6.050 ± 0.158 6.200 ± 0.258
Protein mg/dL N/a N/a
Specific Gravity – 1.029 ± 0.002 1.028 ± 0.003

 

Phenotyping Procedures:

Animal Receipt and Maintenance
A quantity of twenty mice (ten males and ten females) was submitted for testing, strain identified as Line NCR Nude (CrTac:NCR-Foxn1nu), age 7 weeks. Mice were received at RBU 3, Taconic Biotechnology, Albany NY and acclimated for three days on irradiated NIH #31M rodent diet and sterilized water ad lib, sterile contact bedding (paper chip) and a 12:12 light:dark cycle. All animals appeared normal during this period and routine health surveillance of this colony detected no microbial pathogens. Mice were assigned study unique identification numbers (males 1-10, females 11-20).

 

Urinalysis
All mice were fasted in metabolic cages and an overnight urine sample was collected. Urine analysis was performed using Multistix 10 SG (Bayer). Strips were read and recorded as per the manufacturer’s instructions, and the results are presented in Table 2.

 

Clinical Chemistry and Hematology
A terminal blood sample was taken from Carbon Dioxide – anesthetized mice via cardiac puncture. The collected blood was divided into two samples. One sample was treated with EDTA and stored at 4°C for hematological evaluation. Another sample was allowed to clot at 4°C for 30 minutes, and then centrifuged at 7000rpm for 10 minutes, and the serum was decanted and frozen at -80°C for clinical chemistry analysis. A slide smear was made from a single drop of whole blood. Frozen serum, chilled whole blood and slides were delivered to LabCorp (RTP, NC) for analysis; the results are presented in Table 3. Unless otherwise indicated, serum chemistry data is generated from a Hitachi 717 automated analyzer and hematological data is generated from a Celldyne 3500. WBC differential counts are performed manually.

 

Necropsy and Organ Weights
All mice were euthanized and bodyweights were recorded. Representative tissues were collected, weighed, and immersion fixed in 10% Neutral Buffered Formalin. Tissues were delivered to the Taconic lab for histological preparation and evaluation. Tabulation of organ weights is presented in Table 4. The pathologist’s summary and detailed histological descriptions follow.

 

Discussion
All animals were thrifty on arrival and appeared clinically normal. Locomotor behavior was normal and there were no visible lesions or discharges at the mucous membranes. All tissues appeared normal on gross necropsy evaluation and weights were within normal limits. There were no unusual findings upon collection of these tissues nor otherwise observed in the body cavities.

The overall profile of these mice is consistent with expectations of a general-purpose mouse. None of the parameters are indicative of impaired system function.