Gene: 670	Name: Fzd1	Family: GPCR	Subfamily: WNT	Accession: AF054623	GI: 6863202

Gene 670
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 
• Fertility
• Behavioral tests
• Aging studies

Gene 670
Fertility

Both homozygous mutant males and females had possible reduced fertility.  Their progeny that survived were viable until weaning.

Three homozygous mutant mice of each gender were set up in a fertility mating one on one with each other at seven to eighteen weeks of age. Two of the male and female pairs (329429 and 336403, 340957 and 329431) did not produce any litters that were viable at weaning age.  The third pair (340958 and 336405) produced two litters that were viable at weaning age.

Mouse ID numbers are as follows:

3 homozygous mutant males (329429, 340957, 340958)

3 homozygous mutant females (336403, 329431, 336405)

 

 

Gene 670
Expression Summary

Taqman Summary:
The highest levels of RNA transcripts are detectable in lung, kidney, skin, gallbladder, urinary bladder, pituitary gland, adrenal gland, colon, epididymis, seminal vesicle, coagulating gland, prostate gland, ovary, uterus and white fat.
     
Lower levels of RNA transcripts are detectable in whole brain, cortex, subcortical region, cerebellum, brainstem, olfactory bulb, spinal cord, eye, Harderian glands, heart, liver, pancreas, spleen, thymus, lymph nodes, bone marrow, salivary gland, skeletal muscle, tongue, stomach, small intestine, cecum and testis.

LacZ Summary:
LacZ expression was detected in most organs examined.  Most striking expression was detected in the central nervous system, muscularis of the urinary bladder and blood vessels.  Staining was observed in different tissue and cell types, including cardiac muscle, epithelium, neurons, cartilage, adipose tissue and blood vessels.

LacZ expression was detected:  brain, spinal cord, sciatic nerve, eyes, thymus, spleen, lymph nodes, aorta, heart, lung, liver, pancreas, kidney, urinary bladder, thyroid gland, trachea, pituitary gland, adrenal glands, skeletal muscle, skin, testis, prostate gland and ovary.

LacZ expression was not detected in bone marrow.

Gene 670
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. The data were compiled from the N0F2 and N1F2 generations.

49 Day Cohort Mouse ID numbers are as follows:
2 homozygous mutant females (262733, 274060)
3 homozygous mutant males (274056, 298190, 316715)
2 wild-type control females (262729, 262730)
3 wild-type control males (262726, 265146, 273067)

300 Day Cohort Mouse ID numbers are as follows:
2 homozygous mutant females (295853, 295877)
2 homozygous mutant males (295883, 312914)
2 wild-type control females (295854, 295884)
2 wild-type control males (302042, 308890)

Bone Mineral Density (BMD in g/cm² ), fat % (fat percent expressed as a percentage of body soft tissue compartment), and R-value of soft tissue were calculated from Bone Mineral Content (BMC in g), bone and tissue areas (cm² ), and total tissue mass (g) generated by a PIXImus densitometer.

Densitometric Findings:

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 670
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 data were compiled from the N0F2 and N1F2 generations.

49 Day Cohort Mouse ID numbers are as follows:
3 homozygous mutant females (262733, 274060, 307672)
3 homozygous mutant males (274056, 298190, 316715)
2 wild-type control females (262729, 262730)
3 wild-type control males (262726, 265146, 273067)

300 Day Cohort Mouse ID numbers are as follows:
2 homozygous mutant females (295853, 295877)
1 homozygous mutant male (295883)

No Significant Abnormalities:

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

Gene 670
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. The data were compiled from the N0F2 and N1F2 generations.

49 Day Cohort Mouse ID numbers are as follows:
3 homozygous mutant females (262733, 274060, 307672)
3 homozygous mutant males (274056, 298190, 316715)
2 wild-type control females (262729, 262730)
3 wild-type control males (262726, 265146, 273067)

300 Day Cohort Mouse ID numbers are as follows:
2 homozygous mutant females (295853, 295877)
2 homozygous mutant males (295883, 312914)
1 wild-type control male (308890)

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 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, and/or lesions of a nonspecific etiology. They were not considered to be related to genotype.

Body and Organ Weight Findings:

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 670
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 chemistry panel. The data were compiled from the N0F2 and N1F2 generations.

49 Day Cohort Mouse ID numbers are as follows:
3 homozygous mutant females (262733, 274060, 307672)
3 homozygous mutant males (274056, 298190, 316715)
2 wild-type control females (262729, 262730)
2 wild-type control males (265146, 273067)

90 Day Cohort Mouse ID numbers are as follows:
1 homozygous mutant female (308895)
3 homozygous mutant males (312914, 329574, 340951)
3 wild-type control males (308890, 308893, 312900)

180 Day Cohort Mouse ID numbers are as follows:
4 homozygous mutant females (295853, 295877, 298203, 308895)
3 homozygous mutant males (295883, 329574, 340951)
4 wild-type control females (295854, 295884, 295892, 296595)
4 wild-type control males (302042, 308890, 308893, 312900)

300 Day Cohort Mouse ID numbers are as follows:
2 homozygous mutant females (295853, 295877)
2 homozygous mutant males (295883, 312914)
2 wild-type control females (295854, 295884)
2 wild-type control males (308890, 312900)

Values for the various analytes evaluated were generally similar between homozygous 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 670
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. The data were compiled from the N0F2 and N1F2 generations.

49 Day Cohort Mouse ID numbers are as follows:
3 homozygous mutant females (262733, 274060, 307672)
3 homozygous mutant males (274056, 298190, 316715)
2 wild-type control females (262729, 262730)
2 wild-type control males (265146, 273067)

90 Day Cohort Mouse ID numbers are as follows:
2 homozygous mutant females (295853, 295877)
2 homozygous mutant males (322472, 329574)
1 wild-type control female (295854)

180 Day Cohort Mouse ID numbers are as follows:
4 homozygous mutant females (295853, 295877, 298203, 308895)
4 homozygous mutant males (295883, 312914, 329574, 340951)
4 wild-type control females (295854, 295884, 295892, 296595)
2 wild-type control males (302042, 308890)

300 Day Cohort Mouse ID numbers are as follows:
2 homozygous mutant females (295853, 295877)
2 homozygous mutant males (295883, 312914)
2 wild-type control females (295854, 295884)
2 wild-type control males (302042, 308890)

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

Gene 670
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. The data were compiled from the N0F2 and N1F2 generations.

49 Day Cohort Mouse ID numbers are as follows:
3 homozygous mutant females (262733, 274060, 307672)
3 homozygous mutant males (274056, 298190, 316715)
2 wild-type control females (262729, 262730)
3 wild-type control males (262726, 265146, 273067)

300 Day Cohort Mouse ID numbers are as follows:
2 homozygous mutant females (295853, 295877)
2 homozygous mutant males (295883, 312914)
2 wild-type control females (295854, 295884)
2 wild-type control males (302042, 308890)

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, 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, 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. Certain lesions, including an extra digit on a hind foot, are present that occasionally occur spontaneously in mice of this sex and age group.  In this target, such a finding is present in a wild-type control female (262729).  These findings are 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 670
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 (295853, 295877, 298203, 308895)
2 homozygous mutant males (295883, 312914)
4 wild-type control females (295854, 295884, 295892, 296595)
4 wild-type control males (302042, 308890, 308893, 312900)

90 Day Cohort Mouse ID numbers are as follows:
1 homozygous mutant male (329574)

180 Day Cohort Mouse ID numbers are as follows:
2 homozygous mutant females (298203, 308895)
3 homozygous mutant males (312914, 329574, 340951)
1 wild-type control female (296595)
4 wild-type control males (302042, 308890, 308893, 312900)

300 Day Cohort Mouse ID numbers are as follows:
2 homozygous mutant females (298203, 308895)
2 homozygous mutant males (329574, 340951)
2 wild-type control females (295854, 295884)
3 wild-type control males (302042, 308893, 312900)

Body Weight and Length Findings:

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.