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Gene: 1486	Name: Slc22al2	Family: Transporter	Subfamily: Organic cation	Accession: AB005451	GI: 2696708

Gene 1486
Summary of Phenotypic Analysis

There were no significant differences detected in the homozygous mutant mice when compared with age- and gender-matched wild-type control mice.

ES cells derived from the 129/OlaHsd mouse substrain were used to generate chimeric mice. F1 mice were generated by breeding with C57BL/6 females. F2 homozygous mutant mice were produced by intercrossing F1 heterozygous males and females.

Wild-type control mice and homozygous mutant mice were evaluated by the following examinations or tests:

Physical examination
Necropsy, including body length, body weight, and organ weight measurements
Histological examination of tissues and organs
Bone marrow section evaluation
Complete blood counts and differential cell counts
Clinical chemistry panels
Densitometry
Aging studies

Gene 1486
Expression Summary

RT-PCR Summary:
High levels of RNA transcripts are detectable in kidney.

Very low levels of RNA transcripts are also detectable in testis and prostate gland.

No RNA transcripts are detectable in brain, cortex, subcortical region, cerebellum, brainstem, olfactory bulb, spinal cord, eye, Harderian glands, heart, lung, liver, pancreas, spleen, thymus, lymph nodes, bone marrow, skin, gallbladder, urinary bladder, pituitary gland, adrenal gland, salivary gland, skeletal muscle, tongue, stomach, small intestine, large intestine, cecum, epididymis, seminal vesicle, coagulating gland, ovaries, uterus and white fat.

LacZ Summary:
LacZ (beta-galactosidase) expression is detectable in brain, retina, kidney and testis. Very strong X-Gal signals are detectable in the cortex of kidney.

Expression:
Brain
In wholemount staining moderate lacZ expression is detectable in ventricles and cerebellum. On coronal sections weak lacZ expression is detectable in ventricles.

Eyes
Weak lacZ expression is detectable in the inner nuclear and ganglion cell layers of the retina.

Kidney
Very strong lacZ expression is detectable in many tubules of the cortex.

Male Reproductive Systems
Testis
Very weak lacZ expression is detectable in a few spermatogenic cells of the seminiferous tubules.

No Expression:
LacZ expression is not detected in: spinal cord, sciatic nerve, Harderian glands, thymus, lymph nodes, bone marrow, aorta, heart, lung, liver, gallbladder, trachea, larynx, esophagus, thyroid gland, parathyroid gland, pituitary gland, adrenal glands, salivary glands, tongue, skeletal muscle, skin, and female reproductive system.

Gene 1486
Densitometry

There were no significant differences detected in the homozygous mutant mice when compared with age- and gender-matched wild-type control mice.

The following mice were evaluated by dual-energy x-ray absorptiometry.

Densitometric Findings:

When compared to historical but not contemporaneous age- and gender-matched wild-type control mice, total tissue mass and fat % were increased in two 300 day homozygous mutant males. We have not reported these findings as phenotypic changes, but we have presented them here for your consideration.

Other incidental densitometric differences were present between some mice. These findings were considered to represent background differences occasionally seen in this strain of mice, differences due to spontaneous disease, age-related differences, and/or differences of a nonspecific etiology. They were not considered to be genotype related.

Gene 1486
Histopathology

There were no significant differences detected in the homozygous mutant mice when compared with age- and gender-matched wild-type control mice.

Tissues from the following mice were evaluated histologically.

The following tissues were examined and considered to have no genotype-related abnormality: brain, pituitary gland, ears, nasal cavity, salivary glands, oral cavity, lymph nodes, aorta, lungs, gallbladder, pancreas, spleen, kidneys, urinary bladder, stomach, small and large intestines, larynx, esophagus, trachea, thyroid gland, thymus gland, tongue, skeletal muscle, sciatic nerve, mammary glands, vertebrae, spinal cord, bone (skull, sternum, femur, tibia, and stifle joint), reproductive tract (including gonads), eyes, Harderian glands, integumentary system (skin and either clitoral or preputial glands), and bone marrow.

Bone marrow was examined in sections of sternum, vertebrae, and/or femur and tibia. Marrow cellularity, myeloid:erythroid (M:E) ratio, myeloid and erythroid maturation sequences, and numbers of megakaryocytes were evaluated.

Incidental lesions were present in some tissues. These findings were considered to represent background lesions occasionally seen in this strain of mice, lesions due to spontaneous disease, age-related lesions, lesions due to procedural artifacts, and/or lesions of a nonspecific etiology. They were not considered to be genotype related.

Gene 1486
Necropsy

There were no significant differences detected in the homozygous mutant mice when compared with age- and gender-matched wild-type control mice.

The following mice were necropsied. Body weight, body length, and organ weights were obtained, and gross pathological findings were recorded.

49 Day Cohort Mouse ID numbers are as follows:
3 homozygous mutant females (197472, 206851, 209224)
3 homozygous mutant males (197477, 209221, 233070)
2 wild-type control females (197467, 197469)
2 wild-type control males (197474, 197475)

300 Day Cohort Mouse ID numbers are as follows:
2 homozygous mutant females (222048, 239569)
2 homozygous mutant males (255472, 309691)

Mice were examined for the following observables: adrenal glands, body length, body weight, bone marrow, bone - cranium, bone - femur, bone - sternum, bone - stifle joint, bone - vertebral column, brain, cecum, colon, duodenum, epididymis - seminal vesicle, esophagus, eyes, gallbladder, general appearance, Harderian glands, heart, heart weight, ileum, jejunum, kidney weight, kidneys, liver, liver weight, lungs, lymph nodes, mesentery, ovaries, pancreas, penis, salivary glands, sciatic nerve, scrotum, skeletal muscle, skin, skinned mouse, spleen, spleen weight, stomach, testes, testes - epididymis weight, thymus, thymus weight, tongue, trachea, urinary bladder, urine, uterus and vagina. (Gender-specific observables apply to the appropriate gender.)

Necropsy Findings:

There were no genotype-related or biologically significant differences noted between mutant and wild-type control mice for any of the parameters evaluated at necropsy. Incidental lesions may have been present in some tissues. These findings were considered to represent background lesions occasionally seen in this strain of mice, lesions due to spontaneous disease, age-related lesions, lesions due to procedural artifacts, and/or lesions of a nonspecific etiology. They were not considered to be related to genotype.

Body and Organ Weight Findings:

When compared to age- and gender-matched wild-type control mice, body weight was increased in two 300 day homozygous mutant males. We have not reported this findings as a phenotypic changes, but we have presented it here for your consideration.

Other differences in body length, body weight, organ weights, and/or organ weight to body weight ratios were present between individual mice. The variability between mice usually fell within our historical reference ranges and was not correlated with genotype.

Gene 1486
Clinical Chemistry

There were no significant differences in the homozygous mutant mice when compared with age- and gender-matched wild-type control mice.

Serum samples from the following mice were evaluated by a clinical biochemistry panel.

49 Day Cohort Mouse ID numbers are as follows:
3 homozygous mutant females (197472, 206851, 209224)
3 homozygous mutant males (197477, 209221, 233070)
2 wild-type control females (197467, 197469)
2 wild-type control males (197474, 197475)

90 Day Cohort Mouse ID numbers are as follows:
4 homozygous mutant females (222048, 239569, 239570, 255473)
3 homozygous mutant males (255472, 309691, 315938)
3 wild-type control females (255475, 285764, 285766)
4 wild-type control males (285759, 285760, 285761, 285762)

180 Day Cohort Mouse ID numbers are as follows:
3 homozygous mutant females (222048, 239569, 239570)
3 homozygous mutant males (309691, 309695, 315938)
2 wild-type control females (285764, 285766)
4 wild-type control males (285759, 285760, 285761, 285762)

300 Day Cohort Mouse ID numbers are as follows:
2 homozygous mutant females (222048, 239569)
2 homozygous mutant males (255472, 309691)
2 wild-type control females (285764, 285766)
2 wild-type control males (285759, 285760)

When compared to age- and gender-matched wild-type control mice, two 300-day homozygous mutant males (255472, 309691) had increased levels of cholesterol and high density lipoprotein. We are not reporting these findings as phenotypic changes, but we present them here for your consideration.

Values for the other various analytes evaluated were generally similar between mutant and wild-type control mice. Although variations in clinical chemistry values were present in some mice, they were not related to genotype and, thus, were not considered phenotypically relevant.

Gene 1486
Hematology

There were no significant differences in the homozygous mutant mice when compared with age- and gender-matched wild-type control mice.

Blood samples from the following mice were evaluated by a complete blood count and differential cell count.

49 Day Cohort Mouse ID numbers are as follows:
3 homozygous mutant females (197472, 206851, 209224)
3 homozygous mutant males (197477, 209221, 233070)
3 wild-type control females (197466, 197467, 197469)
2 wild-type control males (197474, 197475)

90 Day Cohort Mouse ID numbers are as follows:
4 homozygous mutant females (222048, 239569, 239570, 255473)
1 homozygous mutant male (255472)
3 wild-type control females (255475, 285764, 290253)
4 wild-type control males (285759, 285760, 285761, 285762)

180 Day Cohort Mouse ID numbers are as follows:
4 homozygous mutant females (222048, 239569, 239570, 255473)
3 homozygous mutant males (255472, 309691, 315938)
3 wild-type control females (255475, 285764, 290253)
4 wild-type control males (285759, 285760, 285761, 285762)

300 Day Cohort Mouse ID numbers are as follows:
2 homozygous mutant females (222048, 239569)
2 homozygous mutant males (255472, 309691)
2 wild-type control females (285764, 285766)
2 wild-type control males (285759, 285760)

Although minor variations of hematological values were present in some animals, these changes were not related to genotype and, thus, were not considered phenotypically relevant.

Gene 1486
Physical Examination

There were no significant differences detected in the homozygous mutant mice when compared with age- and gender-matched wild-type control mice.

The following mice were evaluated by physical examination.

49 Day Cohort Mouse ID numbers are as follows:
3 homozygous mutant females (197472, 206851, 209224)
3 homozygous mutant males (197477, 209221, 233070)
2 wild-type control females (197467, 197469)
2 wild-type control males (197474, 197475)

300 Day Cohort Mouse ID numbers are as follows:
2 homozygous mutant females (222048, 239569)
2 homozygous mutant males (255472, 309691)
2 wild-type control females (285764, 285766)
2 wild-type control males (285759, 285760)

Mice were examined in detail as follows: anus, behavior, body shape, claws, coat - fur, coat color - back, coat color - belly, ear - left, ear - right, eye - left, eye - right, eye color - left, eye color - right, feces, feces color, feces exam, forelimb - left, forelimb - right, forelimb number of amputated digits - left, forelimb number of amputated digits - right, forelimb number of digits - left, forelimb number of digits - right, general appearance, genitals - female, genitals - male, hair type, head shape, hindlimb - left, hindlimb - right, hindlimb number of amputated digits - left, hindlimb number of amputated digits - right, hindlimb number of digits - left, hindlimb number of digits - right, injuries, lesions, limb shape, locomotor, lumps - masses, mammary glands, mice in cage, respiration, skin appearance, snout, swelling - joints, tail, teeth color, teeth length, urine, urine color, urine exam, and whiskers. (Gender-specific observables apply to the appropriate gender.)

Individual homozygous mutant mice had only occasional minor differences in observed physical features compared to wild-type control mice These findings were considered to represent individual variability, background features occasionally seen in this strain of mice, findings due to spontaneous disease, age-related findings, and/or findings of a nonspecific etiology. However, none of these differences was regarded as biologically significant or genotype related.

Gene 1486
Aging Metrics

There were no significant differences detected in the homozygous mutant mice when compared with age- and gender-matched wild-type control mice.

Body weights and body lengths were measured for mice at 49, 90, 180, and 300 days of age.

49 Day Cohort Mouse ID numbers are as follows:
4 homozygous mutant females (222048, 239569, 239570, 255473)
3 homozygous mutant males (255472, 309695, 315938)
4 wild-type control females (255475, 285764, 285766, 290253)
4 wild-type control males (285759, 285760, 285761, 285762)

90 Day Cohort Mouse ID numbers are as follows:
4 homozygous mutant females (222048, 239569, 239570, 255473)
1 homozygous mutant male (255472)
4 wild-type control females (255475, 285764, 285766, 290253)
4 wild-type control males (285759, 285760, 285761, 285762)

180 Day Cohort Mouse ID numbers are as follows:
4 homozygous mutant females (222048, 239569, 239570, 255473)
4 homozygous mutant males (255472, 309691, 309695, 315938)
4 wild-type control females (255475, 285764, 285766, 290253)
4 wild-type control males (285759, 285760, 285761, 285762)

300 Day Cohort Mouse ID numbers are as follows:
2 homozygous mutant females (239570, 255473)
2 homozygous mutant males (309695, 315938)
4 wild-type control females (255475, 285764, 285766, 290253)
4 wild-type control males (285759, 285760, 285761, 285762)

Body Weight and Length Findings:

When compared to age- and gender-matched wild-type control mice, body weight was increased in one 90 day female (255473) and two 180 day male (255472, 309691) homozygous mutants. We have not reported these findings as phenotypic changes, but we have presented them here for your consideration.

Other differences in body length and body weight were present between individual mice. The variability between mice usually fell within our historical reference ranges and was not correlated with genotype.